MCID: ATX030
MIFTS: 74

Ataxia-Telangiectasia malady

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Reproductive diseases, Skin diseases, Endocrine diseases, Fetal diseases, Blood diseases, Immune diseases, Cancer diseases

Aliases & Classifications for Ataxia-Telangiectasia

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Aliases & Descriptions for Ataxia-Telangiectasia:

Name: Ataxia-Telangiectasia 49 11 21 22 23 51 67
Ataxia Telangiectasia 32 10 68 45 22 46 47 12 67 36 35 65
Louis-Bar Syndrome 68 21 45 22 23 51 67
Ataxia-Telangiectasia Variant 51 24 65
a-T 68 22 23
Telangiectasia, Cerebello-Oculocutaneous 68 23
at 45 67
Immunodeficiency with Ataxia Telangiectasia 45
 
Cerebello-Oculocutaneous Telangiectasia 45
Ataxia Telangiectasia Syndrome 23
Boder-Sedgwick Syndrome 10
Louis Bar Syndrome 10
V-at 51
Atm 23
At1 67

Characteristics:

Orphanet epidemiological data:

51
ataxia-telangiectasia:
Inheritance: Autosomal recessive; Prevalence: 1-5/10000 (Norway),1-9/1000000 (Norway),1-9/100000 (United States),1-9/1000000 (Europe); Age of onset: Childhood,Infancy; Age of death: adult

HPO:

61
ataxia-telangiectasia:
Inheritance: autosomal recessive inheritance


Classifications:



External Ids:

OMIM49 208900
Disease Ontology10 DOID:12704
MeSH36 D001260
NCIt42 C2887
Orphanet51 100, 370109
SNOMED-CT59 68504005
ICD10 via Orphanet28 G11.3
MESH via Orphanet37 D001260
UMLS via Orphanet66 C0004135
UMLS65 C0004135, C1876175

Summaries for Ataxia-Telangiectasia

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Genetics Home Reference:23 Ataxia-telangiectasia is a rare inherited disorder that affects the nervous system, immune system, and other body systems. This disorder is characterized by progressive difficulty with coordinating movements (ataxia) beginning in early childhood, usually before age 5. Affected children typically develop difficulty walking, problems with balance and hand coordination, involuntary jerking movements (chorea), muscle twitches (myoclonus), and disturbances in nerve function (neuropathy). The movement problems typically cause people to require wheelchair assistance by adolescence. People with this disorder also have slurred speech and trouble moving their eyes to look side-to-side (oculomotor apraxia). Small clusters of enlarged blood vessels called telangiectases, which occur in the eyes and on the surface of the skin, are also characteristic of this condition.

MalaCards based summary: Ataxia-Telangiectasia, also known as ataxia telangiectasia, is related to hypothalamic disease and vascular dementia, and has symptoms including polycystic ovaries, strabismus and nystagmus. An important gene associated with Ataxia-Telangiectasia is ATM (ATM Serine/Threonine Kinase), and among its related pathways are PLK3 signaling events and Aurora A signaling. Affiliated tissues include lung, breast and skin, and related mouse phenotypes are pigmentation and respiratory system.

NIH Rare Diseases:45 Ataxia telangiectasia (a-t) is rare condition that affects the nervous system, the immune system, and many other parts of the body. signs and symptoms of the condition usually begin in early childhood, often before age 5. the condition is typically characterized by cerebellar ataxia (uncoordinated muscle movements), oculomotor apraxia, telangiectasias, choreoathetosis (uncontrollable movements of the limbs), a weakened immune system with frequent infections, and an increased risk of cancers such as leukemia and lymphoma. a-t is caused by changes (mutations) in the atm gene and is inherited in an autosomal recessive manner. treatment is supportive and based on the signs and symptoms present in each person. last updated: 4/5/2016

UniProtKB/Swiss-Prot:67 Ataxia telangiectasia: A rare recessive disorder characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and eyeballs, immunodeficiency, growth retardation and sexual immaturity. Patients have a strong predisposition to cancer; about 30% of patients develop tumors, particularly lymphomas and leukemias. Cells from affected individuals are highly sensitive to damage by ionizing radiation and resistant to inhibition of DNA synthesis following irradiation.

MedlinePlus:35 Ataxia-telangiectasia (a-t) is a rare, inherited disease. it affects the nervous system, immune system, and other body systems. symptoms appear in young children, usually before age 5. they include ataxia - trouble coordinating movements poor balance slurred speech tiny, red spider veins, called telangiectasias, on the skin and eyes lung infections delayed physical and sexual development people with a-t have an increased risk of developing diabetes and cancers, especially lymphoma and leukemia. although it affects the brain, people with a-t usually have normal or high intelligence. a-t has no cure. treatments might improve some symptoms. they include injections to strengthen the immune system, physical and speech therapy, and high-dose vitamins. nih: national institute of neurological disorders and stroke

NINDS:46 Ataxia-telangiectasia is a rare, childhood neurological disorder that causes degeneration in the part of the brain that controls motor movements and speech. The first signs of the disease are unsteady walking and slurred speech, usually occurring during the first five years of life. Telangiectasias (tiny, red "spider" veins), which appear in the corners of the eyes or on the surface of the ears and cheeks, are characteristic of the disease, but are not always present and generally do not appear in the first years of life. About 35 percent of those with A-T develop cancer, most frequently acute lymphocytic leukemia or lymphoma. The most unusual symptom is an acute sensitivity to ionizing radiation, such as X-rays or gamma rays.

OMIM:49 Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases,... (208900) more...

Wikipedia:68 Ataxia telangiectasia (A-T) (also referred to as Louis–Bar syndrome ) is a rare, neurodegenerative,... more...

GeneReviews summary for NBK26468

Related Diseases for Ataxia-Telangiectasia

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Diseases in the Ataxia-Telangiectasia family:

Ataxia-Telangiectasia-Like Disorder

Diseases related to Ataxia-Telangiectasia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50)    (show all 514)
idRelated DiseaseScoreTop Affiliating Genes
1hypothalamic disease30.4BRCA1, CDKN1A, TP53
2vascular dementia30.4AGTR1, BRCA1, TP53
3breast cancer29.5AGTR1, ATM, ATR, BRCA1, CDKN1A, CHEK1
4ataxia-telangiectasia-like disorder12.9
5cytomegalovirus disease in patients with impaired cell mediated immunity deemed at risk12.3
6pulmonary fungal infections in patients deemed at risk12.3
7poliomyelitis in patients with immunodeficiencies deemed at risk12.3
8nijmegen breakage syndrome12.2
9arterial tortuosity syndrome11.9
10ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia11.5
11asphyxiating thoracic dystrophy11.5
12leukemia10.6
13lymphoma10.6
14adenocarcinoma10.6
15endotheliitis10.6
16pancreatic cancer10.5
17liddle syndrome, scnn1b-related10.5CHEK2, TP53
18arthritis10.5
19hepatitis10.5
20prostatitis10.5
21cervicitis10.5
22retinitis10.5
23deep leiomyoma10.5PCNA, TP53
24neuroblastoma10.4
25obesity10.4
26ischemia10.4
27cerebritis10.4
28thyroiditis10.4
29neuropathy10.4
30breast cancer, childhood10.4ATM, BRCA1, CHEK2
31brca2 hereditary breast and ovarian cancer syndrome10.4ATM, BRCA1, CHEK2
32internal auditory canal lipoma10.4ATM, BRCA1, TP53
33common bile duct disease10.4ATM, BRCA1, TP53
34pancreatic cancer 410.4BRCA1, NBN
35synchronous bilateral breast carcinoma10.4ATM, BRCA1, CHEK2
36rheumatoid arthritis10.4
37hiv-110.4
38hepatocellular carcinoma10.4
39renal cell carcinoma10.4
40cataract10.4
41cholangiocarcinoma10.4
42gastric cancer10.4
43oral squamous cell carcinoma10.4
44heart disease10.4
45esophagitis10.4
46dementia10.4
47pancreatitis10.4
48neuronitis10.4
49aneurysm10.4
50pancreatic serous cystadenocarcinoma10.4BRCA1, TP53

Graphical network of the top 20 diseases related to Ataxia-Telangiectasia:



Diseases related to ataxia-telangiectasia

Symptoms for Ataxia-Telangiectasia

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Symptoms by clinical synopsis from OMIM:

208900

Clinical features from OMIM:

208900

Symptoms:

 51 (show all 39)
  • abnormal eye movements/oculomotor disorder
  • strabismus/squint
  • nystagmus
  • anomalies of skin, subcutaneous tissue and mucosae
  • telangiectasiae of the skin
  • telangiectasiae of mucosae
  • premature greying of hair
  • abnormal hepatic enzymes/transaminases
  • repeat respiratory infections
  • thymic aplasia/hypoplasia
  • abnormal/polycystic ovaries
  • late puberty/hypogonadism/hypogenitalism
  • abnormal gait
  • ataxia/incoordination/trouble of the equilibrium
  • movement disorder
  • tremor
  • speech troubles/aphasia/dysphasia/echolalia/mutism/logorrhea/dysprosodia
  • anomalies of the immunitary system
  • immunodeficiency/increased susceptibility to infections/recurrent infections
  • agammaglobulinemia/hypogammaglobulinemia/b-cell deficiency
  • t-cell deficiency/cellular immunity deficiency
  • lymphopenia
  • autosomal recessive inheritance
  • chromosome breakage
  • premature ageing
  • albinism (hair)
  • diabetes mellitus
  • hypertonia/spasticity/rigidity/stiffness
  • seizures/epilepsy/absences/spasms/status epilepticus
  • elocution disorders/dysarthria/dysphonia
  • muscle hypotrophy/atrophy/dystrophy/agenesis/amyotrophy
  • neoplasms/tumors
  • short stature/dwarfism/nanism
  • skin hypoplasia/aplasia/atrophy
  • cafe-au-lait spot
  • small/atrophic/hypoplastic testes/monorchism/microorchidism/anorchia
  • insulin-independent/type 2 diabetes
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • failure to thrive/difficulties for feeding in infancy/growth delay

HPO human phenotypes related to Ataxia-Telangiectasia:

(show all 61)
id Description Frequency HPO Source Accession
1 polycystic ovaries hallmark (90%) HP:0000147
2 strabismus hallmark (90%) HP:0000486
3 nystagmus hallmark (90%) HP:0000639
4 gait disturbance hallmark (90%) HP:0001288
5 tremor hallmark (90%) HP:0001337
6 lymphopenia hallmark (90%) HP:0001888
7 neurological speech impairment hallmark (90%) HP:0002167
8 recurrent respiratory infections hallmark (90%) HP:0002205
9 premature graying of hair hallmark (90%) HP:0002216
10 incoordination hallmark (90%) HP:0002311
11 elevated hepatic transaminases hallmark (90%) HP:0002910
12 abnormality of chromosome stability hallmark (90%) HP:0003220
13 decreased antibody level in blood hallmark (90%) HP:0004313
14 cellular immunodeficiency hallmark (90%) HP:0005374
15 aplasia/hypoplasia of the thymus hallmark (90%) HP:0010515
16 mucosal telangiectasiae hallmark (90%) HP:0100579
17 telangiectasia of the skin hallmark (90%) HP:0100585
18 seizures typical (50%) HP:0001250
19 hypertonia typical (50%) HP:0001276
20 neurological speech impairment typical (50%) HP:0002167
21 neoplasm typical (50%) HP:0002664
22 skeletal muscle atrophy typical (50%) HP:0003202
23 short stature typical (50%) HP:0004322
24 hypopigmentation of hair typical (50%) HP:0005599
25 abnormality of the testis occasional (7.5%) HP:0000035
26 cafe-au-lait spot occasional (7.5%) HP:0000957
27 type ii diabetes mellitus occasional (7.5%) HP:0005978
28 aplasia/hypoplasia of the skin occasional (7.5%) HP:0008065
29 cognitive impairment occasional (7.5%) HP:0100543
30 non-hodgkin lymphoma HP:0012539
31 hodgkin lymphoma HP:0012189
32 abnormal spermatogenesis HP:0008669
33 immunoglobulin igg2 deficiency HP:0008348
34 elevated alpha-fetoprotein HP:0006254
35 decreased number of cd4+ t cells HP:0005407
36 defective b cell differentiation HP:0005357
37 short stature HP:0004322
38 recurrent bronchitis HP:0002837
39 iga deficiency HP:0002720
40 bronchiectasis HP:0002110
41 leukemia HP:0001909
42 lymphopenia HP:0001888
43 abnormality of the hair HP:0001595
44 tremor HP:0001337
45 myoclonus HP:0001336
46 dystonia HP:0001332
47 reduced tendon reflexes HP:0001315
48 choreoathetosis HP:0001266
49 dysarthria HP:0001260
50 ataxia HP:0001251
51 seizures HP:0001250
52 cafe-au-lait spot HP:0000957
53 glucose intolerance HP:0000833
54 delayed puberty HP:0000823
55 diabetes mellitus HP:0000819
56 hypoplasia of the thymus HP:0000778
57 nystagmus HP:0000639
58 conjunctival telangiectasia HP:0000524
59 strabismus HP:0000486
60 sinusitis HP:0000246
61 female hypogonadism HP:0000134

Drugs & Therapeutics for Ataxia-Telangiectasia

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FDA approved drugs:

(show all 174)
id Drug Name Active Ingredient(s)15 Company Approval Date
1
Abraxane15 41 PACLITAXEL Celgene October 2012
FDA Label: Abraxane
Disease/s that Drug Treats:non-small cell lung cancer
Indications and Usage:15 ABRAXANE is a microtubule inhibitor indicated for the treatment of: Metastatic breast cancer, after failure of combination chemotherapyfor metastatic disease or relapse within 6 months of adjuvantchemotherapy. Prior therapy should have included an anthracyclineunless clinically contraindicated. (1.1) Locally advanced or metastatic non-small cell lung cancer (NSCLC),as first-line treatment in combination with carboplatin, in patients whoare not candidates for curative surgery or radiation therapy. (1.2) Metastatic adenocarcinoma of the pancreas as first-line treatment, incombination with gemcitabine. (1.3)
DrugBank Targets:13 1. Apoptosis regulator Bcl-2;;2. Tubulin beta-1 chain;;3. Nuclear receptor subfamily 1 group I member 2;;4. Microtubule-associated protein 4;;5. Microtubule-associated protein 2; ;6. Microtubule-associated protein tau
Mechanism of Action:15 
Target: microtubule
Action: inhibitor
FDA: ABRAXANE is a microtubule inhibitor that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubulesby preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubulenetwork that is essential for vital interphase and mitotic cellular functions. Paclitaxel induces abnormal arrays or “bundles” ofmicrotubules throughout the cell cycle and multiple asters of microtubules during mitosis.
2
Abstral15 FENTANYL (citrate) ProStrakan January 2011
FDA Label: Abstral
Disease/s that Drug Treats:breakthrough cancer pain in opiod-tolerant patients
Indications and Usage:15 ABSTRAL is an opioid agonist indicated for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. (1) Limitations of Use: ABSTRAL may be dispensed only to patients enrolled in the TIRF REMS Access program.
DrugBank Targets:13 1. Mu-type opioid receptor ;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:15 
Target: µ-opioid receptor (possible mechanism of action)
Action: agonist
FDA: Fentanyl is a pure opioid agonist whose principal therapeutic action is analgesia. Other members of the classknown as opioid agonists include substances such as morphine, oxycodone, hydromorphone, codeine, andhydrocodone.
3
Adcetris15 41 BRENTUXIMAB VEDOTIN Seattle Genetics August 2011
FDA Label: Adcetris
Disease/s that Drug Treats:Hodgkin lymphoma and anaplastic large cell lymphoma
Indications and Usage:15 ADCETRIS is a CD30-directed antibody-drug conjugate indicated fortreatment of patients with: Hodgkin lymphoma after failure of autologous stem cell transplant(ASCT) or after failure of at least two prior multi-agent chemotherapyregimens in patients who are not ASCT candidates (1.1). Systemic anaplastic large cell lymphoma after failure of at least oneprior multi-agent chemotherapy regimen (1.2).Accelerated approval was granted for the above indications based onoverall response rate. An improvement in patient-reported outcomes orsurvival has not been established. Continued approval for these indicationsmay be contingent upon verification and description of clinical benefit inconfirmatory trials.
DrugBank Targets:13 Tumor necrosis factor receptor superfamily member 8
Mechanism of Action:15 
Target: microtubule
Action: disruptor
FDA: Brentuximab vedotin is an ADC. The antibody is a chimeric IgG1 directed against CD30. Thesmall molecule, MMAE, is a microtubule disrupting agent. MMAE is covalently attached to theantibody via a linker. Nonclinical data suggest that the anticancer activity of ADCETRIS is dueto the binding of the ADC to CD30-expressing cells, followed by internalization of theADC-CD30 complex, and the release of MMAE via proteolytic cleavage. Binding of MMAE totubulin disrupts the microtubule network within the cell, subsequently inducing cell cycle arrestand apoptotic death of the cells.
4
Afinitor 15 41 EVEROLIMUS Novartis March 2009
FDA Label: Afinitor
Disease/s that Drug Treats:renal cell carcinoma/ renal angiomyolipoma associated with tuberous sclerosis complex/ advanced pancreatic neuroendocrine tumors/ hormone receptor-positive, HER2-negative breast cancer
Indications and Usage:15 AFINITOR is a kinase inhibitor indicated for the treatment of: postmenopausal women with advanced hormone receptor-positive, HER2- negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole. (1.1) adults with progressive neuroendocrine tumors of pancreatic origin (PNET) that are unresectable, locally advanced or metastatic. AFINITOR is not indicated for the treatment of patients with functional carcinoid tumors. (1.2) adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. (1.3) adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. The effectiveness of AFINITOR in the treatment of renal angiomyolipoma is based on an analysis of durable objective responses in patients treated for a median of 8.3 months. Further follow-up of patients is required to determine long-term outcomes. (1.4) AFINITOR and AFINITOR DISPERZ are kinase inhibitors indicated for the treatment of: pediatric and adult patients with tuberous sclerosis complex (TSC) who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. The effectiveness is based on demonstration of durable objective response, as evidenced by reduction in SEGA tumor volume. Improvement in diseaserelated symptoms and overall survival in patients with SEGA and TSC has not been demonstrated. (1.5)
DrugBank Targets:13 Serine/threonine-protein kinase mTOR
Mechanism of Action:15 
Target: mTOR
Action: inhibitor
FDA: Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of thePI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers. Everolimus binds to an intracellularprotein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex 1 (mTORC1) and thus inhibition ofmTOR kinase activity. Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic initiationfactor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis. S6K1 is a substrate ofmTORC1 and phosphorylates the activation domain 1 of the estrogen receptor which results in ligand-independentactivation of the receptor. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) andreduced the expression of vascular endothelial growth factor (VEGF). Inhibition of mTOR by everolimus has been shownto reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies.Constitutive activation of the PI3K/Akt/mTOR pathway can contribute to endocrine resistance in breast cancer. In vitrostudies show that estrogen-dependent and HER2+ breast cancer cells are sensitive to the inhibitory effects of everolimus,and that combination treatment with everolimus and Akt, HER2, or aromatase inhibitors enhances the anti-tumor activityof everolimus in a synergistic manner.Two regulators of mTORC1 signaling are the oncogene suppressors tuberin-sclerosis complexes 1 and 2 (TSC1, TSC2).Loss or inactivation of either TSC1 or TSC2 leads to activation of downstream signaling. In TSC, a genetic disorder,inactivating mutations in either the TSC1 or the TSC2 gene lead to hamartoma formation throughout the body.
5
Alimta15 41 PEMETREXED (also Pemetrexed Disodium) Eli Lilly February 2004
FDA Label: Alimta
Disease/s that Drug Treats:Mesothelioma
Indications and Usage:15 ALIMTA® is a folate analog metabolic inhibitor indicated for: Locally Advanced or Metastatic Nonsquamous Non-Small CellLung Cancer: Initial treatment in combination with cisplatin. (1.1) Maintenance treatment of patients whose disease has notprogressed after four cycles of platinum-based first-linechemotherapy. (1.2) After prior chemotherapy as a single-agent. (1.3) Mesothelioma: in combination with cisplatin. (1.4)Limitations of Use: ALIMTA is not indicated for the treatment of patients withsquamous cell non-small cell lung cancer. (1.5)
DrugBank Targets:13 1. Thymidylate synthase;2. Bifunctional purine biosynthesis protein PURH;3. Dihydrofolate reductase;4. Trifunctional purine biosynthetic protein adenosine-3
Mechanism of Action:15 
Target: folic acid/ thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase
Action: antagonist/ inhibitor
FDA: ALIMTA, pemetrexed for injection, is a folate analog metabolic inhibitor that exerts its action by disrupting folatedependentmetabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibitsthymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT),which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides.Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate bindingprotein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzymefolylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT.Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, is thought to occur to alesser extent, in normal tissues. Polyglutamated metabolites are thought to have an increased intracellular half-liferesulting in prolonged drug action in malignant cells.
6
Aloxi15 41 PALONOSETRON (hydrochloride) MGI Pharma, Helsinn Healthcare August 2003
FDA Label: Aloxi
Disease/s that Drug Treats:Chemotherapy side effects
Indications and Usage:15 ALOXI is a serotonin-3 (5-HT3) receptor antagonist indicated in adults for: Moderately emetogenic cancer chemotherapy -- prevention ofacute and delayed nausea and vomiting associated with initial andrepeat courses (1.1) Highly emetogenic cancer chemotherapy -- prevention of acutenausea and vomiting associated with initial and repeat courses(1.1) Prevention of postoperative nausea and vomiting (PONV) for upto 24 hours following surgery. Efficacy beyond 24 hours has notbeen demonstrated (1.3)ALOXI is indicated in pediatric patients aged 1 month to less than 17 yearsfor: Prevention of acute nausea and vomiting associated with initialand repeat courses of emetogenic cancer chemotherapy, includinghighly emetogenic cancer chemotherapy (1.2)
DrugBank Targets:13 5-hydroxytryptamine receptor 3A
Mechanism of Action:15 
Target: serotonin subtype 3 (5-HT3) receptor/ ion channels involved in ventricular polarization
Action: antagonist/ blocker
FDA: Palonosetron is a 5-HT3 receptor antagonist with a strong bindingaffinity for this receptor and little or no affinity for other receptors.Cancer chemotherapy may be associated with a high incidence ofnausea and vomiting, particularly when certain agents, such as cisplatin, areused. 5-HT3 receptors are located on the nerve terminals of the vagus in theperiphery and centrally in the chemoreceptor trigger zone of the areapostrema. It is thought that chemotherapeutic agents produce nausea andvomiting by releasing serotonin from the enterochromaffin cells of the smallintestine and that the released serotonin then activates 5-HT3 receptorslocated on vagal afferents to initiate the vomiting reflex.Postoperative nausea and vomiting is influenced by multiple patient,surgical and anesthesia related factors and is triggered by release of 5-HT ina cascade of neuronal events involving both the central nervous system andthe gastrointestinal tract. The 5-HT3 receptor has been demonstrated toselectively participate in the emetic response.
7
Aredia15 41 PAMIDRONATE DISODIUM Chiron August 1996
FDA Label: Aredia
Disease/s that Drug Treats:osteolytic bone metastases of breast cancer
Indications and Usage:15 Hypercalcemia of MalignancyAredia, in conjunction with adequate hydration, is indicated for the treatment of moderate or severehypercalcemia associated with malignancy, with or without bone metastases. Patients who have eitherepidermoid or non-epidermoid tumors respond to treatment with Aredia. Vigorous saline hydration, anintegral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made torestore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia maybe treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patientsshould be hydrated adequately throughout the treatment, but overhydration, especially in those patientswho have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction ofhypovolemia. The safety and efficacy of Aredia in the treatment of hypercalcemia associated withhyperparathyroidism or with other non-tumor-related conditions has not been established.Paget’s DiseaseAredia is indicated for the treatment of patients with moderate to severe Paget’s disease of bone. Theeffectiveness of Aredia was demonstrated primarily in patients with serum alkaline phosphatase ≥3 timesthe upper limit of normal. Aredia therapy in patients with Paget’s disease has been effective in reducingserum alkaline phosphatase and urinary hydroxyproline levels by ≥50% in at least 50% of patients, and by≥30% in at least 80% of patients. Aredia therapy has also been effective in reducing these biochemicalmarkers in patients with Paget’s disease who failed to respond, or no longer responded to othertreatments.Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of MultipleMyelomaAredia is indicated, in conjunction with standard antineoplastic therapy, for the treatment of osteolyticbone metastases of breast cancer and osteolytic lesions of multiple myeloma. The Aredia treatment effectappeared to be smaller in the study of breast cancer patients receiving hormonal therapy than in the studyof those receiving chemotherapy, however, overall evidence of clinical benefit has been demonstrated(see CLINICAL PHARMACOLOGY, Osteolytic Bone Metastases of Breast Cancer and OsteolyticLesions of Multiple Myeloma, Clinical Trials section).
DrugBank Targets:13 1. Farnesyl pyrophosphate synthase;2. Hydroxylapatite
Mechanism of Action:15 
Target: bone resorption; FPP synthase
Action: inhibitor
FDA: The principal pharmacologic action of Aredia is inhibition of bone resorption. Although the mechanism ofantiresorptive action is not completely understood, several factors are thought to contribute to this action.Aredia adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolutionof this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activitycontributes to inhibition of bone resorption. In animal studies, at doses recommended for the treatment ofhypercalcemia, Aredia inhibits bone resorption apparently without inhibiting bone formation andmineralization. Of relevance to the treatment of hypercalcemia of malignancy is the finding that Arediainhibits the accelerated bone resorption that results from osteoclast hyperactivity induced by varioustumors in animal studies.
8
Aromasin Tablets15 41 EXEMESTANE Pharmacia & Upjohn October 21. 1999
FDA Label: Aromasin Tablets
Disease/s that Drug Treats:advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy
Indications and Usage:15 AROMASIN is an aromatase inhibitor indicated for: Incidences of cardiac ischemic events (myocardial infarction, angina, adjuvant treatment of postmenopausal women with estrogen-receptor and myocardial ischemia) were AROMASIN 1.6%, tamoxifen 0.6%.positive early breast cancer who have received two to three years of Incidence of cardiac failure: AROMASIN 0.4%, tamoxifen 0.3% (6,tamoxifen and are switched to AROMASIN for completion of a total of 6.1).five consecutive years of adjuvant hormonal therapy (14.1). Advanced breast cancer: Most common adverse events were mild to treatment of advanced breast cancer in postmenopausal women whose moderate and included hot flushes (13% vs. 5%), nausea (9% vs. 5%),disease has progressed following tamoxifen therapy (14.2).
DrugBank Targets:13 Cytochrome P450 19A1
Mechanism of Action:15 
Target: steroidal aromatase
Action: inactivator
FDA: Breast cancer cell growth may be estrogen-dependent. Aromatase is the principal enzyme that convertsandrogens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarilyestradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausalwomen is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens(estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromataseinhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breastcancer.Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrateandrostenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that bindsirreversibly to the active site of the enzyme, causing its inactivation, an effect also known as “suicide inhibition.”Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has nodetectable effect on adrenal biosynthesis of corticosteroids or aldosterone. Exemestane has no effect on otherenzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibitingthe aromatase enzyme.
9
Arranon15 41 NELARABINE GlaxoSmithKline October 2005
FDA Label: Arranon
Disease/s that Drug Treats:Lymphoblastic Leukemia
Indications and Usage:15 ARRANON is a nucleoside metabolic inhibitor indicated for the treatment ofpatients with T-cell acute lymphoblastic leukemia and T-cell lymphoblasticlymphoma whose disease has not responded to or has relapsed followingtreatment with at least two chemotherapy regimens. This use is based on theinduction of complete responses. Randomized trials demonstrating increasedsurvival or other clinical benefit have not been conducted. (1)
DrugBank Targets:13 DNA
Mechanism of Action:15 
Target: DNA synthesis
Action: disruptor --> apoptosis
FDA: Nelarabine is a pro-drug of the deoxyguanosine analogue 9-β-D-arabinofuranosylguanine266 (ara-G), a nucleoside metabolic inhibitor. Nelarabine is demethylated by adenosine deaminase267 (ADA) to ara-G, mono-phosphorylated by deoxyguanosine kinase and deoxycytidine kinase, and268 subsequently converted to the active 5’-triphosphate, ara-GTP. Accumulation of ara-GTP in269 leukemic blasts allows for incorporation into deoxyribonucleic acid (DNA), leading to inhibition270 of DNA synthesis and cell death. Other mechanisms may contribute to the cytotoxic and271 systemic toxicity of nelarabine.
apoptosis
Medilexicon: Arranon is a prodrug of the cytotoxic deoxyguanosine analogue 9-ß-D-arabinofuranosylguanine (ara-G). The drug is ultimately metabolized into the active 5'-triphosphate ara-GTP, which disrupts DNA synthesis and induces apoptosis. Additional cytotoxic activities may exist, but these are not fully understood.
FDA: Nelarabine is a pro-drug of the deoxyguanosine analogue 9-β-D-arabinofuranosylguanine266 (ara-G), a nucleoside metabolic inhibitor. Nelarabine is demethylated by adenosine deaminase267 (ADA) to ara-G, mono-phosphorylated by deoxyguanosine kinase and deoxycytidine kinase, and268 subsequently converted to the active 5’-triphosphate, ara-GTP. Accumulation of ara-GTP in269 leukemic blasts allows for incorporation into deoxyribonucleic acid (DNA), leading to inhibition270 of DNA synthesis and cell death. Other mechanisms may contribute to the cytotoxic and271 systemic toxicity of nelarabine.
Drug info:
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10
Arzerra15 41 OFATUMUMAB GlaxoSmithKline October 2009
FDA Label: Arzerra
Disease/s that Drug Treats:chronic lymphocytic leukemia
Indications and Usage:15 ARZERRA (ofatumumab) is a CD20-directed cytolytic monoclonal antibodyindicated: in combination with chlorambucil, for the treatment of previouslyuntreated patients with chronic lymphocytic leukemia (CLL) for whomfludarabine-based therapy is considered inappropriate. (1.1) for the treatment of patients with CLL refractory to fludarabine andalemtuzumab. (1.2)
DrugBank Targets:13 no entry
Mechanism of Action:15 
Target: B-cell
Action: promotes lysis
FDA: Ofatumumab binds specifically to both the small and large extracellular loops of the CD20402 molecule. The CD20 molecule is expressed on normal B lymphocytes (pre-B- to mature403 B-lymphocyte) and on B-cell CLL. The CD20 molecule is not shed from the cell surface and is404 not internalized following antibody binding.405406 The Fab domain of ofatumumab binds to the CD20 molecule and the Fc domain mediates407 immune effector functions to result in B-cell lysis in vitro. Data suggest that possible408 mechanisms of cell lysis include complement-dependent cytotoxicity and antibody-dependent,409 cell-mediated cytotoxicity.
11
Avastin15 41 BEVACIZUMAB Genentech July 2009
FDA Label: Avastin
Disease/s that Drug Treats:renal cell carcinoma & Colorectal Cancer
Indications and Usage:15 Avastin is a vascular endothelial growth factor-specific angiogenesisinhibitor indicated for the treatment of: Metastatic colorectal cancer, with intravenous 5-fluorouracil-basedchemotherapy for first- or second-line treatment. (1.1) Metastatic colorectal cancer, with fluoropyrimidine- irinotecan- orfluoropyrimidine-oxaliplatin-based chemotherapy for second-linetreatment in patients who have progressed on a first-line Avastincontainingregimen. (1.1) Non-squamous non-small cell lung cancer, with carboplatin and paclitaxelfor first line treatment of unresectable, locally advanced, recurrent ormetastatic disease. (1.2) Glioblastoma, as a single agent for adult patients with progressive diseasefollowing prior therapy. (1.3)-Effectiveness based on improvement in objective response rate. No dataavailable demonstrating improvement in disease-related symptoms orsurvival with Avastin. Metastatic renal cell carcinoma with interferon alfa (1.4) Cervical cancer, in combination with paclitaxel and cisplatin or paclitaxeland topotecan in persistent, recurrent, or metastatic disease. (1.5) Platinum-resistant recurrent epithelial ovarian, fallopian tube or primaryperitoneal cancer, in combination with paclitaxel, pegylated liposomaldoxorubicin or topotecan (1.6) Limitation of Use: Avastin is not indicated for adjuvant treatment of coloncancer. (1.1)
DrugBank Targets:13 1. Vascular endothelial growth factor A;2. Low affinity immunoglobulin gamma Fc region receptor III-B;3. Complement C1r subcomponent;4. Complement C1q subcomponent subunit A;5. Complement C1q subcomponent subunit B;6. Complement C1q subcomponent subunit C;7. Low affinity immunoglobulin gamma Fc region receptor III-A;8. High affinity immunoglobulin gamma Fc receptor I;9. Low affinity immunoglobulin gamma Fc region receptor II-a;10. Low affinity immunoglobulin gamma Fc region receptor II-b;11. Low affinity immunoglobulin gamma Fc region receptor II-c
Mechanism of Action:15 
Target: VEGF
Action: inhibitor
FDA: Bevacizumab binds VEGF and prevents the interaction of VEGF to its receptors (Flt-1 and KDR)697 on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial698 cell proliferation and new blood vessel formation in in vitro models of angiogenesis. Administration699 of bevacizumab to xenotransplant models of colon cancer in nude (athymic) mice caused reduction700 of microvascular growth and inhibition of metastatic disease progression
12
Beleodaq15 41 BELINOSTAT Spectrum Pharmaceuticals July 2014
FDA Label: Beleodaq
Disease/s that Drug Treats:relapsed or refractory peripheral T-cell lymphoma
Indications and Usage:15 Beleodaq is a histone deacetylase inhibitor indicated for the treatment ofpatients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Thisindication is approved under accelerated approval based on tumor responserate and duration of response. An improvement in survival or disease-relatedsymptoms has not been established. Continued approval for this indicationmay be contingent upon verification and description of clinical benefit in theconfirmatory trial. (1)
DrugBank Targets:13 no entry
Mechanism of Action:15 
Target: histone deacetylase (HDAC)
Action: inhibitor
FDA: Beleodaq is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from thelysine residues of histones and some non-histone proteins. In vitro, belinostat caused the accumulation ofacetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells.Belinostat shows preferential cytotoxicity towards tumor cells compared to normal cells. Belinostat inhibitedthe enzymatic activity of histone deacetylases at nanomolar concentrations (<250 nM).
13
Bexxar15 41 TOSITUMOMAB; IODINE I 131 TOSITUMOMAB Corixa June 2003
FDA Label: Bexxar
Disease/s that Drug Treats:Non-Hodgkin's Lymphoma
Indications and Usage:15 BEXXAR (tositumomab and Iodine I 131 tositumomab) is a CD20-directedradiotherapeutic antibody indicated for the treatment of patients with CD20-positive, relapsed or refractory, low-grade, follicular, or transformed nonHodgkin'slymphoma who have progressed during or after rituximab therapy,including patients with rituximab-refractory non-Hodgkin's lymphoma. (1.1)Determination of the effectiveness of the BEXXAR therapeutic regimen isbased on overall response rates in patients whose disease is refractory tochemotherapy and rituximab. The effects of the BEXXAR therapeuticregimen on survival are not known. (1.1)Important Limitation of Use BEXXAR therapeutic regimen is only indicated for a single course oftreatment and is not indicated for a first-line treatment. (1.2)
DrugBank Targets:13 1. B-lymphocyte antigen CD20;2. Low affinity immunoglobulin gamma Fc region receptor III-B;3. Complement C1r subcomponent;4. Complement C1q subcomponent subunit A;5. Complement C1q subcomponent subunit B;6. Complement C1q subcomponent subunit C;7. Low affinity immunoglobulin gamma Fc region receptor III-A;8. High affinity immunoglobulin gamma Fc receptor I;9. Low affinity immunoglobulin gamma Fc region receptor II-a;10.Low affinity immunoglobulin gamma Fc region receptor II-b;11. Low affinity immunoglobulin gamma Fc region receptor II-c
Mechanism of Action:15 
Target: CD20
Action: cytotoxic antibody
FDA: Tositumomab binds specifically to an epitope within the extracellular domain of the586 CD20 molecule. The CD20 molecule is expressed on normal B lymphocytes (pre-B lymphocytes587 to mature B lymphocytes) and on B-cell non-Hodgkin's lymphomas. The CD20 molecule is not588 shed from the cell surface and is not internalized following antibody binding. The BEXXAR589 therapeutic regimen induces cell death by emitting ionizing radiation to CD20-expressing590 lymphocytes or neighboring cells. In addition to cell death mediated by the radioisotope, other591 possible mechanisms of action include antibody-dependent cellular cytotoxicity, complement-592 dependent cytotoxicity, and CD20-mediated apoptosis.
14
Blincyto15 41 BLINATUMOMAB Amgen December 2014
FDA Label: Blincyto
Disease/s that Drug Treats:Philadelphia chromosome-negative relapsed /refractory B cell precursor acute lymphoblastic leukemia
Indications and Usage:15 BLINCYTO is a bispecific CD19-directed CD3 T-cell engager indicated forthe treatment of Philadelphia chromosome-negative relapsed or refractory Bcellprecursor acute lymphoblastic leukemia (ALL). This indication isapproved under accelerated approval. Continued approval for this indicationmay be contingent upon verification of clinical benefit in subsequent trials. (1)
DrugBank Targets:13 1. B-lymphocyte antigen CD19;2. T-cell surface glycoprotein CD3 delta chain
Mechanism of Action:15 
Target: CD19-directed CD3 T-cell
Action: engager
FDA: Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on thesurface of cells of B-lineage origin and CD3 expressed on the surface of T cells. It activates endogenousT cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant Bcells. Blinatumomab mediates the formation of a synapse between the T cell and the tumor cell,upregulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatorycytokines, and proliferation of T cells, which result in redirected lysis of CD19+ cells.
15
Bosulif15 41 BOSUTINIB MONOHYDRATE Pfizer September 2012
FDA Label: Bosulif
Disease/s that Drug Treats:Ph+ chronic myelogenous leukemia
Indications and Usage:15 BOSULIF is a kinase inhibitor indicated for the treatment of adult patientswith chronic, accelerated, or blast phase Ph+ chronic myelogenous leukemia(CML) with resistance or intolerance to prior therapy. (1)
DrugBank Targets:13 1. Breakpoint cluster region protein;2. Tyrosine-protein kinase ABL1;3. Tyrosine-protein kinase Lyn;4. Tyrosine-protein kinase HCK;5. Proto-oncogene tyrosine-protein kinase Src;6. Cyclin-dependent kinase 2;7. Dual specificity mitogen-activated protein kinase kinase 1;8. Dual specificity mitogen-activated protein kinase kinase 2;9. Mitogen-activated protein kinase kinase kinase 2;10. Calcium/calmodulin-dependent protein kinase type II subunit gamma
Mechanism of Action:15 
Target: tyrosine kinase/ Src-family kinases including Src, Lyn, and Hck
Action: inhibitor
FDA: Bosutinib is a tyrosine kinase inhibitor. Bosutinib inhibits the Bcr-Abl kinase that promotes CML; it is also aninhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms ofBcr-Abl expressed in murine myeloid cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells. In mice,treatment with bosutinib reduced the size of CML tumors relative to controls and inhibited growth of murine myeloidtumors expressing several imatinib-resistant forms of Bcr-Abl.
16
Busulfex15 41 BUSULFAN Orphan Medical February 1999
FDA Label: Busulfex
Disease/s that Drug Treats:leukemia
Indications and Usage:15 BUSULFEX is an alkylating drug indicated for: Use in combination with cyclophosphamide as a conditioning regimenprior to allogeneic hematopoietic progenitor cell transplantation forchronic myelogenous leukemia (CML) (1)
DrugBank Targets:13 DNA
Mechanism of Action:15 
Target: DNA
Action: alkylyzer
FDA: Busulfan is a bifunctional alkylating agent in which two labile methanesulfonate groups are attached to opposite ends of afour-carbon alkyl chain. In aqueous media, busulfan hydrolyzes to release the methanesulfonate groups. This producesreactive carbonium ions that can alkylate DNA. DNA damage is thought to be responsible for much of the cytotoxicity ofbusulfan.
17
CEA-Scan15 Immunomedics April 1996
FDA Label: -
Disease/s that Drug Treats:colorectal cancer
Indications and Usage:15 -
DrugBank Targets:13 1. Carcinoembryonic antigen-related cell adhesion molecule 1
Mechanism of Action:15 
Target: carcinoembryonic antigen (""CEA"")
Action: marks
FDA: -
18
Cervarix15 41 Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant GlaxoSmithKline October 2009
FDA Label: -
Disease/s that Drug Treats:prevention of cervical cancer and cervical intraepithelial neoplasia caused by HPV types 16 and 18
Indications and Usage:15 -
DrugBank Targets: -
Mechanism of Action:15 
Target: IgG neutralizing antibodies directed against HPV-L1 capsid proteins
Action: activates/ provokes production
FDA: -
19
Clolar15 41 CLOFARABINE Genzyme December, 2004
FDA Label: Clolar
Disease/s that Drug Treats:Lymphoblastic Leukemia
Indications and Usage:15 Clolar (clofarabine) injection is a purine nucleoside metabolic inhibitorindicated for the treatment of pediatric patients 1 to 21 years old with relapsedor refractory acute lymphoblastic leukemia after at least two prior regimens.This indication is based upon response rate. There are no trials verifying animprovement in disease-related symptoms or increased survival with Clolar.(1)
DrugBank Targets:13 1. DNA polymerase alpha catalytic subunit;2. Ribonucleoside-diphosphate reductase large subunit;3. DNA
Mechanism of Action:15 
Target: ribonucleotide reductase
Action: inhibitor
FDA: Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite bydeoxycytidine kinase and mono- and di-phospho-kinases to the active 5’-triphosphate metabolite.Clofarabine has affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equalto or greater than that of the natural substrate, deoxycytidine. Clofarabine inhibits DNA synthesisby decreasing cellular deoxynucleotide triphosphate pools through an inhibitory action onribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair throughincorporation into the DNA chain by competitive inhibition of DNA polymerases. The affinity ofclofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosinetriphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNArepair by incorporation into the DNA chain during the repair process. Clofarabine 5’-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of thepro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading toprogrammed cell death.Clofarabine is cytotoxic to rapidly proliferating and quiescent cancer cell types in vitro.
20
Cometriq15 41 CABOZANTINIB S-MALATE Exelixis November 2012
FDA Label: Cometriq
Disease/s that Drug Treats:thyroid cancer
Indications and Usage:15 COMETRIQ is a kinase inhibitor indicated for the treatment ofpatients with progressive, metastatic medullary thyroid cancer(MTC). (1)
DrugBank Targets:13 1. Hepatocyte growth factor receptor;2. Vascular endothelial growth factor receptor 2;3. Proto-oncogene tyrosine-protein kinase receptor Ret
Mechanism of Action:15 
Target: tyrosine kinase activity of RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, and TIE-2
Action: inhibitor
FDA: In vitro biochemical and/or cellular assays have shown that cabozantinib inhibits the tyrosinekinase activity of RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, and TIE-2.These receptor tyrosine kinases are involved in both normal cellular function and pathologicprocesses such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumormicroenvironment.
21
Degarelix15 41 degarelix Ferring Pharmaceuticals December of 2008
FDA Label: -
Disease/s that Drug Treats:Prostate Cancer
Indications and Usage:15 -
DrugBank Targets:13 1. Gonadotropin-releasing hormone receptor
Mechanism of Action:15 
Target: Gonadotropin-releasing hormone (GnRH) receptor
Action: antagonist
FDA: -
22
Doxil15 41 DOXORUBICIN HYDROCHLORIDE Alza June 1999
FDA Label: Doxil
Disease/s that Drug Treats:ovarian cancer that is refractory to other first-line therapies
Indications and Usage:15 DOXIL is an anthracycline topoisomerase II inhibitor indicated for: Ovarian cancer (1.1)After failure of platinum-based chemotherapy. AIDS-related Kaposi’s Sarcoma (1.2)After failure of prior systemic chemotherapy or intolerance to such therapy. Multiple Myeloma (1.3)In combination with bortezomib in patients who have not previouslyreceived bortezomib and have received at least one prior therapy.
DrugBank Targets:13 1. DNA;2. DNA topoisomerase 2-alpha
Mechanism of Action:15 
Target: nucleic acidsynthesis
Action: inhibitor
FDA: The active ingredient of DOXIL is doxorubicin HCl. The mechanism of action ofdoxorubicin HCl is thought to be related to its ability to bind DNA and inhibit nucleic acidsynthesis. Cell structure studies have demonstrated rapid cell penetration and perinuclearReference ID: 373359617 chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, andinduction of mutagenesis and chromosomal aberrations.
23
Elitek15 41 RASBURICASE sanofi-aventis October 2009
FDA Label: Elitek
Disease/s that Drug Treats:management of plasma uric acid levels in adults with malignancies
Indications and Usage:15 Elitek is a recombinant urate-oxidase indicated for initial management ofplasma uric acid levels in pediatric and adult patients with leukemia,lymphoma, and solid tumor malignancies who are receiving anti-cancertherapy expected to result in tumor lysis and subsequent elevation of plasmauric acid (1).Limitation of use: Elitek is indicated only for a single course of treatment (1).
DrugBank Targets:13 1. Uric acid
Mechanism of Action:15 
Target: uric acid
Action: converter to alantoin
FDA: In humans, uric acid is the final step in the catabolic pathway of purines. Rasburicase catalyzesenzymatic oxidation of poorly soluble uric acid into an inactive and more soluble metabolite(allantoin).
24
Eloxatin15 41 OXALIPLATIN Sanofi-aventis August 2002
FDA Label: Eloxatin
Disease/s that Drug Treats:Metastatic colon or rectum carcinomas that have recurred or progressed within six months folowing first-line treatment
Indications and Usage:15 ELOXATIN is a platinum-based drug used in combination with infusional 5-fluorouracil /leucovorin, which is indicated for: adjuvant treatment of stage III colon cancer in patients who haveundergone complete resection of the primary tumor. (1) treatment of advanced colorectal cancer. (1)
DrugBank Targets:13 1. DNA
Mechanism of Action:15 
Target: DNA replication and transcription
Action: inhibitor
FDA: Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives viadisplacement of the labile oxalate ligand. Several transient reactive species are formed, includingmonoaquo and diaquo DACH platinum, which covalently bind with macromolecules. Both interandintrastrand Pt-DNA crosslinks are formed. Crosslinks are formed between the N7 positions oftwo adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by anintervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription.Cytotoxicity is cell-cycle nonspecific.In vivo studies have shown antitumor activity of oxaliplatin against colon carcinoma. Incombination with 5-fluorouracil, oxaliplatin exhibits in vitro and in vivo antiproliferative activitygreater than either compound alone in several tumor models [HT29 (colon), GR (mammary), andL1210 (leukemia)].
25
Erwinaze15 41 asparaginase Erwinia chrysanthemi Eusa Pharma November of 2011
FDA Label: Erwinaze
Disease/s that Drug Treats:acute lymphoblastic leukemia
Indications and Usage:15 ERWINAZE (asparaginase Erwinia chrysanthemi) is an asparagine specificenzyme indicated as a component of a multi-agent chemotherapeutic regimenfor the treatment of patients with acute lymphoblastic leukemia (ALL) whohave developed hypersensitivity to E. coli-derived asparaginase. (1)
DrugBank Targets:13 -
Mechanism of Action:15 
Target: deamidation of asparagine to aspartic acid and ammonia
Action: catalyzer
FDA: Asparaginase Erwinia chrysanthemi catalyzes the deamidation of asparagine to aspartic acid and ammonia, resultingin a reduction in circulating levels of asparagine. The mechanism of action of ERWINAZE is thought to be based onthe inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity, resulting incytotoxicity specific for leukemic cells that depend on an exogenous source of amino acid asparagine for theirprotein metabolism and survival.
26
Ethyol15 AMIFOSTINE Alza December 8, 1995
FDA Label: Ethyol
Disease/s that Drug Treats:ovarian cancer
Indications and Usage:15 ETHYOL (amifostine) is indicated to reduce the cumulative renal toxicity associated withrepeated administration of cisplatin in patients with advanced ovarian cancer.ETHYOL is indicated to reduce the incidence of moderate to severe xerostomia in patientsundergoing post-operative radiation treatment for head and neck cancer, where the radiationport includes a substantial portion of the parotid glands (see Clinical Studies).For the approved indications, the clinical data do not suggest that the effectiveness of cisplatin basedchemotherapy regimens or radiation therapy is altered by ETHYOL. There are at present only limiteddata on the effects of ETHYOL on the efficacy of chemotherapy or radiotherapy in other settings.ETHYOL should not be administered to patients in other settings where chemotherapy can produce asignificant survival benefit or cure, or in patients receiving definitive radiotherapy, except in thecontext of a clinical study (see WARNINGS).
DrugBank Targets:13 1. Ectonucleotide pyrophosphatase/phosphodiesterase family member 1;2. Alkaline phosphatase, placental-like
Mechanism of Action:15 
Target: -
Action: -
FDA: -
27
Eulexin15 FLUTAMIDE Schering-Plough June 1996
FDA Label: Eulexin
Disease/s that Drug Treats:prostate cancer
Indications and Usage:15 EULEXIN capsules are indicated for use in combination with LHRH agonists for the management of locally confined Stage B2C and Stage D2 metastatic carcinoma of the prostate. Stage B2C Prostatic Carcinoma: Treatment with EUlEXIN an the goserelin acetate implant shouls start 8 weeks prior to initiating radiation therapy and continue during radiation therapy. Stage D2 Metastatic Carcinoma: To acheive benefit from treatment, EULEXIN Capsules should be initiated with the LHRH-agonist and continued until progression.
DrugBank Targets:13 1. Androgen receptor;2. Aryl hydrocarbon receptor
Mechanism of Action:15 
Target: androgen uptake and/or nuclear binding of angrogen in target tissues
Action: inhibitor
FDA: In animal studies, flutamide demonstrates potent anti-angrogenic effects. It exerts an antiandrogenic action by inhibiting angrogen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, eg. castration. Elevations of plasma testosterone and estraidiol levels have been noted following flutamide administration.
28
Evista15 41 RALOXIFENE HYDROCHLORIDE Eli Lilly September 2007
FDA Label: Evista
Disease/s that Drug Treats:osteoporosis and reduction of breast cancer risk in postmenopausal women
Indications and Usage:15 EVISTA is an estrogen agonist/antagonist indicated for Treatment and prevention of osteoporosis in postmenopausal women.(1.1)
DrugBank Targets:13 1. Estrogen receptor;2. Estrogen receptor beta
Mechanism of Action:15 
Target: estrogenic pathways
Action: can be an activator or antooagonist
FDA: Decreases in estrogen levels after oophorectomy or menopause lead to increases in bone resorption andaccelerated bone loss. Bone is initially lost rapidly because the compensatory increase in bone formation isinadequate to offset resorptive losses. In addition to loss of estrogen, this imbalance between resorption andformation may be due to age-related impairment of osteoblasts or their precursors. In some women, these changeswill eventually lead to decreased bone mass, osteoporosis, and increased risk for fractures, particularly of the spine,hip, and wrist. Vertebral fractures are the most common type of osteoporotic fracture in postmenopausal women.The biological actions of raloxifene are largely mediated through binding to estrogen receptors. This bindingresults in activation of certain estrogenic pathways and blockade of others. Thus, raloxifene is an estrogenagonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM).Raloxifene decreases resorption of bone and reduces biochemical markers of bone turnover to thepremenopausal range. These effects on bone are manifested as reductions in the serum and urine levels of boneturnover markers, decreases in bone resorption based on radiocalcium kinetics studies, increases in bone mineraldensity (BMD), and decreases in incidence of fractures.
29
Farydak15 41 PANOBINOSTAT LACTATE Novartis February 2015
FDA Label: Farydak
Disease/s that Drug Treats:Multiple myeloma
Indications and Usage:15 FARYDAK, a histone deacetylase inhibitor, in combination with bortezomiband dexamethasone, is indicated for the treatment of patients with multiplemyeloma who have received at least 2 prior regimens, including bortezomiband an immunomodulatory agent. This indication is approved underaccelerated approval based on progression free survival. Continued approvalfor this indication may be contingent upon verification and description ofclinical benefit in confirmatory trials. (1)
DrugBank Targets: -
Mechanism of Action:15 
Target: histone deacetylase (HDAC)
Action: inhibitor
FDA: FARYDAK is a histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDACs atnanomolar concentrations. HDACs catalyze the removal of acetyl groups from the lysine residues of histonesand some non-histone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins,an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. In vitro,Reference ID: 3699607 panobinostat caused the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/orapoptosis of some transformed cells. Increased levels of acetylated histones were observed in xenografts frommice that were treated with panobinostat. Panobinostat shows more cytotoxicity towards tumor cells comparedto normal cells.
30
Faslodex15 41 FULVESTRANT AstraZeneca April 2002
FDA Label: Faslodex
Disease/s that Drug Treats:Hormone receptor positive metastatic breast cancer
Indications and Usage:15 FASLODEX is an estrogen receptor antagonist indicated for the: Treatment of hormone receptor positive metastatic breast cancer inpostmenopausal women with disease progression followingantiestrogen therapy.
DrugBank Targets:13 1. Estrogen receptor
Mechanism of Action:15 
Target: estrogen receptors on tumor cells
Action: antagonist
FDA: Many breast cancers have estrogen receptors (ER) and thegrowth of these tumors can be stimulated by estrogen.Fulvestrant is an estrogen receptor antagonist that binds to theestrogen receptor in a competitive manner with affinitycomparable to that of estradiol and downregulates the ERprotein in human breast cancer cells.In vitro studies demonstrated that fulvestrant is a reversibleinhibitor of the growth of tamoxifen-resistant, as well asestrogen-sensitive human breast cancer (MCF-7) cell lines. Inin vivo tumor studies, fulvestrant delayed the establishment oftumors from xenografts of human breast cancer MCF-7 cellsin nude mice. Fulvestrant inhibited the growth of establishedMCF-7 xenografts and of tamoxifen-resistant breast tumorxenografts.Fulvestrant showed no agonist-type effects in in vivouterotropic assays in immature or ovariectomized mice andrats. In in vivo studies in immature rats and ovariectomizedmonkeys, fulvestrant blocked the uterotrophic action ofestradiol. In postmenopausal women, the absence of changesin plasma concentrations of FSH and LH in response tofulvestrant treatment (250 mg monthly) suggests no peripheralsteroidal effects.
31
Feridex I.V.15 FERUMOXIDES Advanced Magnetics February 1996
FDA Label: -
Disease/s that Drug Treats:liver cancer
Indications and Usage:15 -
DrugBank Targets: -
Mechanism of Action:15 
Target: -
Action: -
FDA: -
32
Folotyn15 41 PRALATREXATE Allos Therapeutics September 2009
FDA Label: Folotyn
Disease/s that Drug Treats:peripheral T-cell lymphoma
Indications and Usage:15 FOLOTYN is a folate analog metabolic inhibitor indicated for the treatment ofpatients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Thisindication is based on overall response rate. Clinical benefit such asimprovement in progression-free survival or overall survival has not beendemonstrated. (1)
DrugBank Targets:13 1. Dihydrofolate reductase;2. Thymidylate synthase
Mechanism of Action:15 
Target: dihydrofolate reductase
Action: inhibitor
FDA: Pralatrexate is a folate analog metabolic inhibitor that competitively inhibits dihydrofolate reductase. It is also acompetitive inhibitor for polyglutamylation by the enzyme folylpolyglutamyl synthetase. This inhibition resultsin the depletion of thymidine and other biological molecules the synthesis of which depends on single carbontransfer.
33
Fusilev15 LEVOLEUCOVORIN CALCIUM Spectrum Pharmaceuticals March of 2008
FDA Label: Fusilev
Disease/s that Drug Treats:rescue after high-dose methotrexate therapy in osteosarcoma and to reduce the toxicity of methotrexate
Indications and Usage:15 Fusilev is a folate analog indicated for: Rescue after high-dose methotrexate therapy in osteosarcoma. Diminishing the toxicity and counteracting the effects of impairedmethotrexate elimination and of inadvertent overdosage of folic acidantagonists. Use in combination chemotherapy with 5-fluorouracil in the palliativetreatment of patients with advanced metastatic colorectal cancer.(1)Limitations of UseFusilev is not approved for pernicious anemia and megaloblastic anemias.Improper use may cause a hematologic remission while neurologicmanifestations continue to progress. (1.1)
DrugBank Targets:13 1. Thymidylate synthase
Mechanism of Action:15 
Target: therapeutic and toxic effects of folic acidantagonists / therapeutic and toxic effects of fluoropyrimidines used in cancer therapy
Action: counteract/enhance
FDA: 12.1.1 Levoleucovorin effects during high-dose methotrexate therapyLevoleucovorin is the pharmacologically active isomer of 5-formyl tetrahydrofolic acid. Levoleucovorin does not requirereduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of “onecarbon”moieties. Administration of levoleucovorin can counteract the therapeutic and toxic effects of folic acidantagonists such as methotrexate, which act by inhibiting dihydrofolate reductase.12.1.2 Levoleucovorin effects in combination with 5-fluorouracilLevoleucovorin can enhance the therapeutic and toxic effects of fluoropyrimidines used in cancer therapy such as5-fluorouracil. 5-fluorouracil is metabolized to 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), which binds to andinhibits thymidylate synthase (an enzyme important in DNA repair and replication). Levoleucovorin is readily convertedto another reduced folate, 5,10-methylenetetrahydrofolate, which acts to stabilize the binding of FdUMP to thymidylatesynthase and thereby enhances the inhibition of this enzyme.
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Gardasil15 41 quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine Merck June 2006
FDA Label: Gardasil
Disease/s that Drug Treats:Cervical Cancer Caused by Human Papillomavirus
Indications and Usage:15 GARDASIL is a vaccine indicated in girls and women 9 through 26years of age for the prevention of the following diseases caused byHuman Papillomavirus (HPV) types included in the vaccine: Cervical, vulvar, vaginal, and anal cancer caused by HPV types 16and 18 (1.1) Genital warts (condyloma acuminata) caused by HPV types 6 and11 (1.1)And the following precancerous or dysplastic lesions caused by HPVtypes 6, 11, 16, and 18: Cervical intraepithelial neoplasia (CIN) grade 2/3 and Cervicaladenocarcinoma in situ (AIS) (1.1) Cervical intraepithelial neoplasia (CIN) grade 1 (1.1) Vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3 (1.1) Vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3 (1.1) Anal intraepithelial neoplasia (AIN) grades 1, 2, and 3 (1.1)GARDASIL is indicated in boys and men 9 through 26 years of age forthe prevention of the following diseases caused by HPV types includedin the vaccine: Anal cancer caused by HPV types 16 and 18 (1.2) Genital warts (condyloma acuminata) caused by HPV types 6 and11 (1.2)And the following precancerous or dysplastic lesions caused by HPVtypes 6, 11, 16, and 18: Anal intraepithelial neoplasia (AIN) grades 1, 2, and 3. (1.2)Limitations of GARDASIL Use and Effectiveness: GARDASIL does not eliminate the necessity for women tocontinue to undergo recommended cervical cancer screening.(1.3, 17) Recipients of GARDASIL should not discontinue anal cancerscreening if it has been recommended by a health care provider.(1.3, 17) GARDASIL has not been demonstrated to provide protectionagainst disease from vaccine and non-vaccine HPV types to whicha person has previously been exposed through sexual activity.(1.3, 14.4, 14.5) GARDASIL is not intended to be used for treatment of activeexternal genital lesions; cervical, vulvar, vaginal, and analcancers; CIN; VIN; VaIN, or AIN. (1.3) GARDASIL has not been demonstrated to protect againstdiseases due to HPV types not contained in the vaccine. (1.3,14.4, 14.5) Not all vulvar, vaginal, and anal cancers are caused by HPV, andGARDASIL protects only against those vulvar, vaginal, and analcancers caused by HPV 16 and 18. (1.3) GARDASIL does not protect against genital diseases not causedby HPV. (1.3) Vaccination with GARDASIL may not result in protection in allvaccine recipients. (1.3) GARDASIL has not been demonstrated to prevent HPV-relatedCIN 2/3 or worse in women older than 26 years of age. (14.7)
DrugBank Targets: -
Mechanism of Action:15 
Target: humoral immune response
Action: inducer
FDA: HPV only infects human beings. Animal studies with analogous animal papillomaviruses suggest thatthe efficacy of L1 VLP vaccines may involve the development of humoral immune responses. Humanbeings develop a humoral immune response to the vaccine, although the exact mechanism of protectionis unknown.
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Gazyva15 41 OBINUTUZUMAB Genentech October of 2013
FDA Label: Gazyva
Disease/s that Drug Treats:previously untreated chronic lymphocytic leukemia
Indications and Usage:15 GAZYVA (obinutuzumab) is a CD20-directed cytolytic antibody and isindicated, in combination with chlorambucil, for the treatment of patients withpreviously untreated chronic lymphocytic leukemia. (1, 14)
DrugBank Targets:13 1. B-lymphocyte antigen CD20
Mechanism of Action:15 
Target: CD20 antigen expressed on the surface of pre B- and mature B-lymphocytes
Action: engager of immune cells and/or activator of intracellular death signaling pathways and/or activator of the complement cascade
FDA: Obinutuzumab is a monoclonal antibody that targets the CD20 antigen expressed on the surfaceof pre B- and mature B-lymphocytes. Upon binding to CD20, obinutuzumab mediates B-celllysis through (1) engagement of immune effector cells, (2) by directly activating intracellulardeath signaling pathways and/or (3) activation of the complement cascade. The immune effectorcell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependentcellular phagocytosis.
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Gemzar15 41 GEMCITABINE HYDROCHLORIDE Eli Lilly May 1996
FDA Label: Gemzar
Disease/s that Drug Treats:pancreatic cancer/Lung cancer
Indications and Usage:15 Gemzar® is a nucleoside metabolic inhibitor indicated: in combination with carboplatin, for the treatment of advanced ovariancancer that has relapsed at least 6 months after completion of platinumbasedtherapy (1.1) in combination with paclitaxel, for first-line treatment of metastaticbreast cancer after failure of prior anthracycline-containing adjuvantchemotherapy, unless anthracyclines were clinically contraindicated(1.2) in combination with cisplatin for the treatment of non-small cell lungcancer (1.3) as a single agent for the treatment of pancreatic cancer (1.4)
DrugBank Targets:13 1. DNA;2. Ribonucleoside-diphosphate reductase large subunit;3. Thymidylate synthase;4. UMP-CMP kinase
Mechanism of Action:15 
Target: ribonucleotide reductase
Action: inhibitor
FDA: Gemcitabine kills cells undergoing DNA synthesis and blocks the progression of cells through the G1/S-phase boundary.Gemcitabine is metabolized by nucleoside kinases to diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. Gemcitabinediphosphate inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate deoxynucleosidetriphosphates for DNA synthesis, resulting in reductions in deoxynucleotide concentrations, including dCTP. Gemcitabinetriphosphate competes with dCTP for incorporation into DNA. The reduction in the intracellular concentration of dCTP by the actionof the diphosphate enhances the incorporation of gemcitabine triphosphate into DNA (self-potentiation). After the gemcitabinenucleotide is incorporated into DNA, only one additional nucleotide is added to the growing DNA strands, which eventually results inthe initiation of apoptotic cell death.
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Gilotrif15 41 AFATINIB DIMALEATE Boehringer Ingelheim July 2013
FDA Label: Gilotrif
Disease/s that Drug Treats:metastatic non-small cell lung cancer with EGFR mutations
Indications and Usage:15 GILOTRIF is a kinase inhibitor indicated for the first-line treatment ofpatients with metastatic non-small cell lung cancer (NSCLC) whose tumorshave epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21(L858R) substitution mutations as detected by an FDA-approved test (1)Limitation of Use: Safety and efficacy of GILOTRIF have not beenestablished in patients whose tumors have other EGFR mutations (1)
DrugBank Targets:13 1. Epidermal growth factor receptor;2. Receptor tyrosine-protein kinase erbB-2;3. Receptor tyrosine-protein kinase erbB-4
Mechanism of Action:15 
Target: tyrosine kinase autophosphorylation
Action: inhibitor
FDA: Afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) andirreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling.Afatinib demonstrated inhibition of autophosphorylation and in vitro proliferation of cell lines expressing wildtypeEGFR or those expressing selected EGFR exon 19 deletion mutations or exon 21 L858R mutations,including some with a secondary T790M mutation, at afatinib concentrations achieved, at least transiently, inpatients. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2.Treatment with afatinib resulted in inhibition of tumor growth in nude mice implanted with tumors eitheroverexpressing wild type EGFR or HER2 or in an EGFR L858R/T790M double mutant model.
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Gliadel Wafer15 41 CARMUSTINE Rhone-Poulenc Rorer, Guilford Pharmaceuticals February 1997
FDA Label: Gliadel Wafer
Disease/s that Drug Treats:brain cancer
Indications and Usage:15 GLIADELWaferisanalkylatingdrugindicatedforthetreatmentof: newly-diagnosedhigh-grade-malignantgliomaasanadjuncttosurgeryandradiation(1)and recurrentglioblastomamultiformeasanadjuncttosurgery(1)
DrugBank Targets:13 1. Glutathione reductase, mitochondrial;2. DNA;3. RNA
Mechanism of Action:15 
Target: DNA and RNA
Action: alkylating agent
FDA: The activity of GLIADEL Wafer is due to release of cytotoxic concentrations of carmustine, aDNA and RNA alkylating agent, into the tumor resection cavity. On exposure to the aqueousenvironment of the resection cavity, the anhydride bonds in the copolymer are hydrolyzed,releasing carmustine, carboxyphenoxypropane, and sebacic acid into the surrounding braintissue.
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Halaven15 41 ERIBULIN MESYLATE Eisai November 2010
FDA Label: Halaven
Disease/s that Drug Treats:metastatic breast cancer
Indications and Usage:15 HALAVEN is a microtubule inhibitor indicated for the treatment ofpatients with metastatic breast cancer who have previously receivedat least two chemotherapeutic regimens for the treatment ofmetastatic disease. Prior therapy should have included ananthracycline and a taxane in either the adjuvant or metastaticsetting (1)
DrugBank Targets:13 -
Mechanism of Action:15 
Target: microtubule dynamics
Action: inhibitor
FDA: Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesterstubulin into nonproductive aggregates. Eribulin exerts its effects via a tubulin-based antimitoticmechanism leading to G 2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic celldeath after prolonged mitotic blockage
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Herceptin15 41 TRASTUZUMAB Genentech October 1998
FDA Label: Herceptin
Disease/s that Drug Treats:Breast cancer/gastric cancer
Indications and Usage:15 Herceptin is a HER2/neu receptor antagonist indicated for: the treatment of HER2 overexpressing breast cancer (1.1, 1.2). the treatment of HER2-overexpressing metastatic gastric orgastroesophageal junction adenocarcinoma (1.3)
DrugBank Targets:13 1. Receptor tyrosine-protein kinase erbB-2;2. Epidermal growth factor receptor;3. Complement C1r subcomponent;4. Complement C1q subcomponent subunit A;5. Complement C1q subcomponent subunit B;6. Complement C1q subcomponent subunit C;7. Complement C1s subcomponent;8. High affinity immunoglobulin gamma Fc receptor I;9. Low affinity immunoglobulin gamma Fc region receptor II-a;10. Low affinity immunoglobulin gamma Fc region receptor II-b;11. Low affinity immunoglobulin gamma Fc region receptor II-c;12. Low affinity immunoglobulin gamma Fc region receptor III-B;13. Low affinity immunoglobulin gamma Fc region receptor III-A
Mechanism of Action:15 
Target: human epidermal growth factor receptor 2 protein (HER2)
Action: binds with strong affinity for immune response
FDA: The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, which is structurally related to the epidermal growth factor receptor. Herceptin has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2. Herceptin is a mediator of antibody-dependent cellular cytotoxicity (ADCC). In vitro, Herceptin-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.
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Ibrance15 41 PALBOCICLIB Pfizer February 2015
FDA Label: Ibrance
Disease/s that Drug Treats:ER-positive, HER2-negative breast cancer
Indications and Usage:15 IBRANCE is a kinase inhibitor indicated in combination with letrozole for thetreatment of postmenopausal women with estrogen receptor (ER)-positive,human epidermal growth factor receptor 2 (HER2)-negative advanced breastcancer as initial endocrine-based therapy for their metastatic disease. Thisindication is approved under accelerated approval based on progression-freesurvival (PFS). Continued approval for this indication may be contingentupon verification and description of clinical benefit in a confirmatory trial. (1)
DrugBank Targets:13 1. Cyclin-dependent kinase 4;2. Cyclin-dependent kinase 6
Mechanism of Action:15 
Target: cyclin-dependent kinase (CDK) 4 and 6
Action: inhibitor
FDA: Palbociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. Cyclin D1 and CDK4/6 aredownstream of signaling pathways which lead to cellular proliferation. In vitro, palbociclib reducedcellular proliferation of estrogen receptor (ER)-positive breast cancer cell lines by blocking progressionof the cell from G1 into S phase of the cell cycle. Treatment of breast cancer cell lines with thecombination of palbociclib and antiestrogens leads to decreased retinoblastoma protein (Rb)phosphorylation resulting in reduced E2F expression and signaling and increased growth arrestcompared to treatment with each drug alone. In vitro treatment of ER-positive breast cancer cell lineswith the combination of palbociclib and antiestrogens leads to increased cell senescence, which wassustained for up to 6 days following drug removal. In vivo studies using a patient-derived ER-positivebreast cancer xenograft model demonstrated that the combination of palbociclib and letrozole increasedthe inhibition of Rb phosphorylation, downstream signaling and tumor growth compared to each drugalone.
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Iclusig15 41 PONATINIB HYDROCHLORIDE Ariad Pharmaceuticals December 2012
FDA Label: Iclusig
Disease/s that Drug Treats:chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia
Indications and Usage:15 Iclusig is a kinase inhibitor indicated for the: Treatment of adult patients with T315I-positive chronic myeloidleukemia (chronic phase, accelerated phase, or blast phase) or T315IpositivePhiladelphia chromosome positive acute lymphoblasticleukemia (Ph+ ALL). Treatment of adult patients with chronic phase, accelerated phase, orblast phase chronic myeloid leukemia or Ph+ ALL for whom no othertyrosine kinase inhibitor (TKI) therapy is indicated. (1)These indications are based upon response rate. There are no trials verifying animprovement in disease-related symptoms or increased survival with Iclusig.
DrugBank Targets:13 1. Tyrosine-protein kinase ABL1;2. Breakpoint cluster region protein;3. Mast/stem cell growth factor receptor Kit;4. Proto-oncogene tyrosine-protein kinase receptor Ret;5. Angiopoietin-1 receptor;6. Receptor-type tyrosine-protein kinase FLT3;7. Fibroblast growth factor receptor 1;8. Fibroblast growth factor receptor 2;9. Fibroblast growth factor receptor 3;10. Fibroblast growth factor receptor 4;11. Tyrosine-protein kinase Lck;12. Proto-oncogene tyrosine-protein kinase Src;13. Tyrosine-protein kinase Lyn;14. Vascular endothelial growth factor receptor 2;15. Platelet-derived growth factor receptor alpha
Mechanism of Action:15 
Target: tyrosine kinase activity of ABL and T315I mutant ABL
Action: inhibitor
FDA: Ponatinib is a kinase inhibitor. Ponatinib inhibited the in vitro tyrosine kinase activity of ABL and T315I mutant ABL withIC50 concentrations of 0.4 and 2.0 nM, respectively. Ponatinib inhibited the in vitro activity of additional kinases with IC50concentrations between 0.1 and 20 nM, including members of the VEGFR, PDGFR, FGFR, EPH receptors and SRCfamilies of kinases, and KIT, RET, TIE2, and FLT3. Ponatinib inhibited the in vitro viability of cells expressing native ormutant BCR-ABL, including T315I. In mice, treatment with ponatinib reduced the size of tumors expressing native orT315I mutant BCR-ABL when compared to controls.
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Imbruvica15 41 IBRUTINIB Pharmacyclics November of 2013/ February 2014
FDA Label: Imbruvica
Disease/s that Drug Treats:mantle cell lymphoma/chronic lymphocytic leukemia
Indications and Usage:15 IMBRUVICA is a kinase inhibitor indicated for the treatment of patients with: Mantle cell lymphoma (MCL) who have received at least one priortherapy (1.1).Accelerated approval was granted for this indication based on overallresponse rate. Continued approval for this indication may be contingentupon verification of clinical benefit in confirmatory trials. Chronic lymphocytic leukemia (CLL) who have received at least oneprior therapy (1.2). Chronic lymphocytic leukemia with 17p deletion (1.3). Waldenström’s macroglobulinemia (WM) (1.4).
DrugBank Targets:13 1. Tyrosine-protein kinase BTK
Mechanism of Action:15 
Target: Bruton's tyrosine kinase (Btk)
Action: selective inhibitor
FDA: Ibrutinib is a small-molecule inhibitor of BTK. Ibrutinib forms a covalent bond with a cysteineresidue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is asignaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. BTK’srole in signaling through the B-cell surface receptors results in activation of pathways necessaryfor B-cell trafficking, chemotaxis, and adhesion. Nonclinical studies show that ibrutinib inhibitsmalignant B-cell proliferation and survival in vivo as well as cell migration and substrateadhesion in vitro.
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Inlyta15 41 AXITINIB Pfizer January 2012
FDA Label: Inlyta
Disease/s that Drug Treats:advanced renal cell carcinoma
Indications and Usage:15 INLYTA is a kinase inhibitor indicated for the treatment of advancedrenal cell carcinoma after failure of one prior systemic therapy. (1)
DrugBank Targets:13 1. Vascular endothelial growth factor receptor 1;2. Vascular endothelial growth factor receptor 2;3. Vascular endothelial growth factor receptor 3
Mechanism of Action:15 
Target: receptor tyrosine kinases
Action: inhibitor
FDA: Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growthfactor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. Thesereceptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGFmediatedendothelial cell proliferation and survival were inhibited by axitinib in vitro and in mousemodels. Axitinib was shown to inhibit tumor growth and phosphorylation of VEGFR-2 in tumor xenograftmouse models.
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Intron A15 41 INTERFERON ALFA-2B Schering-Plough December 1997/ December 1995/ March 1997
FDA Label: Intron A
Disease/s that Drug Treats:non-Hodgkin's lymphoma/ malignant melanoma / Hepatitis C
Indications and Usage:15 Hairy Cell Leukemia INTRON® A is indicated for the treatment of patients 18 years ofage or older with hairy cell leukemia.Malignant Melanoma INTRON A is indicated as adjuvant to surgical treatment inpatients 18 years of age or older with malignant melanoma who are free of disease butat high risk for systemic recurrence, within 56 days of surgery.Follicular Lymphoma INTRON A is indicated for the initial treatment of clinicallyaggressive (see Clinical Pharmacology) follicular Non-Hodgkin’s Lymphoma inconjunction with anthracycline-containing combination chemotherapy in patients 18years of age or older. Efficacy of INTRON A therapy in patients with low-grade, lowtumorburden follicular Non-Hodgkin’s Lymphoma has not been demonstrated.Condylomata Acuminata INTRON A is indicated for intralesional treatment of selectedpatients 18 years of age or older with condylomata acuminata involving externalsurfaces of the genital and perianal areas (see DOSAGE AND ADMINISTRATION).The use of this product in adolescents has not been studied.AIDS-Related Kaposi's Sarcoma INTRON A is indicated for the treatment of selectedpatients 18 years of age or older with AIDS-Related Kaposi's Sarcoma. The likelihoodof response to INTRON A therapy is greater in patients who are without systemic symptoms, who have limited lymphadenopathy and who have a relatively intact immunesystem as indicated by total CD4 count.Chronic Hepatitis C INTRON A is indicated for the treatment of chronic hepatitis C inpatients 18 years of age or older with compensated liver disease who have a history ofblood or blood-product exposure and/or are HCV antibody positive. Studies in thesepatients demonstrated that INTRON A therapy can produce clinically meaningful effectson this disease, manifested by normalization of serum alanine aminotransferase (ALT)and reduction in liver necrosis and degeneration.A liver biopsy should be performed to establish the diagnosis of chronic hepatitis.Patients should be tested for the presence of antibody to HCV. Patients with othercauses of chronic hepatitis, including autoimmune hepatitis, should be excluded. Priorto initiation of INTRON A therapy, the physician should establish that the patient hascompensated liver disease. The following patient entrance criteria for compensated liverdisease were used in the clinical studies and should be considered before INTRON Atreatment of patients with chronic hepatitis C: No history of hepatic encephalopathy, variceal bleeding, ascites, or otherclinical signs of decompensation Bilirubin Less than or equal to 2 mg/dL Albumin Stable and within normal limits Prothrombin Time Less than 3 seconds prolonged WBC Greater than or equal to 3000/mm3 Platelets Greater than or equal to 70,000/mm3Serum creatinine should be normal or near normal.Prior to initiation of INTRON A therapy, CBC and platelet counts should beevaluated in order to establish baselines for monitoring potential toxicity. These testsshould be repeated at Weeks 1 and 2 following initiation of INTRON A therapy, andmonthly thereafter. Serum ALT should be evaluated at approximately 3-month intervalsto assess response to treatment (see DOSAGE AND ADMINISTRATION).Patients with preexisting thyroid abnormalities may be treated if thyroidstimulatinghormone (TSH) levels can be maintained in the normal range by medication.TSH levels must be within normal limits upon initiation of INTRON A treatment and TSHtesting should be repeated at 3 and 6 months (see PRECAUTIONS, LaboratoryTests).INTRON A in combination with REBETOL® is indicated for the treatment ofchronic hepatitis C in patients 3 years of age and older with compensated liver diseasepreviously untreated with alpha interferon therapy and in patients 18 years of age andolder who have relapsed following alpha interferon therapy. See REBETOL prescribinginformation for additional information. Chronic Hepatitis B INTRON A is indicated for the treatment of chronic hepatitis B inpatients 1 year of age or older with compensated liver disease. Patients who have beenserum HBsAg positive for at least 6 months and have evidence of HBV replication(serum HBeAg positive) with elevated serum ALT are candidates for treatment. Studiesin these patients demonstrated that INTRON A therapy can produce virologic remissionof this disease (loss of serum HBeAg) and normalization of serum aminotransferases.INTRON A therapy resulted in the loss of serum HBsAg in some responding patients.Prior to initiation of INTRON A therapy, it is recommended that a liver biopsy beperformed to establish the presence of chronic hepatitis and the extent of liver damage.The physician should establish that the patient has compensated liver disease. Thefollowing patient entrance criteria for compensated liver disease were used in theclinical studies and should be considered before INTRON A treatment of patients withchronic hepatitis B: No history of hepatic encephalopathy, variceal bleeding, ascites, or othersigns of clinical decompensation Bilirubin Normal Albumin Stable and within normal limits Prothrombin Time Adults less than 3 seconds prolongedPediatrics less than or equal to 2 seconds prolonged WBC Greater than or equal to 4000/mm3 Platelets Adults greater than or equal to 100,000/mm3Pediatrics greater than or equal to 150,000/mm3Patients with causes of chronic hepatitis other than chronic hepatitis B or chronichepatitis C should not be treated with INTRON A. CBC and platelet counts should beevaluated prior to initiation of INTRON A therapy in order to establish baselines formonitoring potential toxicity. These tests should be repeated at treatment Weeks 1, 2,4, 8, 12, and 16. Liver function tests, including serum ALT, albumin, and bilirubin,should be evaluated at treatment Weeks 1, 2, 4, 8, 12, and 16. HBeAg, HBsAg, andALT should be evaluated at the end of therapy, as well as 3- and 6-months posttherapy,since patients may become virologic responders during the 6-month periodfollowing the end of treatment. In clinical studies in adults, 39% (15/38) of respondingpatients lost HBeAg 1 to 6 months following the end of INTRON A therapy. Ofresponding patients who lost HBsAg, 58% (7/12) did so 1 to 6 months post-treatment.A transient increase in ALT greater than or equal to 2 times baseline value (flare)can occur during INTRON A therapy for chronic hepatitis B. In clinical trials in adultsand pediatrics, this flare generally occurred 8 to 12 weeks after initiation of therapy andwas more frequent in responders (adults 63%, 24/38; pediatrics 59%, 10/17) than innonresponders (adults 27%, 13/48; pediatrics 35%, 19/55). However, in adults andpediatrics, elevations in bilirubin greater than or equal to 3 mg/dL (greater than or equalto 2 times ULN) occurred infrequently (adults 2%, 2/86; pediatrics 3%, 2/72) duringtherapy. When ALT flare occurs, in general, INTRON A therapy should be continued unless signs and symptoms of liver failure are observed. During ALT flare, clinicalsymptomatology and liver function tests including ALT, prothrombin time, alkalinephosphatase, albumin, and bilirubin, should be monitored at approximately 2-weekintervals (see WARNINGS).
DrugBank Targets:13 1. Interferon alpha/beta receptor 2;2. Interferon alpha/beta receptor 1
Mechanism of Action:15 
Target: intracellular oncogene expression, natural killer and cytotoxic T-cells, microphage, cytokine production
Action: stimulation, induction (unspecified effects on oncogene expression)
FDA: -
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Iressa15 41 GEFITINIB AstraZeneca May 2003
FDA Label: Iressa
Disease/s that Drug Treats:Non-Small-Cell Lung Cancer
Indications and Usage:15 IRESSA is indicated as monotherapy for the continued treatment of patients with locally advanced ormetastatic non-small cell lung cancer after failure of both platinum-based and docetaxelchemotherapies who are benefiting or have benefited from IRESSA.In light of positive survival data with other agents including another oral EGFR inhibitor, physiciansshould use other treatment options in advanced non-small cell lung cancer patient populations whohave received one or two prior chemotherapy regimens and are refractory or intolerant to their mostrecent regimen. The effectiveness of IRESSA was initially based on objective response rates (see CLINICALPHARMACOLOGY-Clinical Studies section). Subsequent studies intended to demonstrate anincrease in survival have been unsuccessful. Specifically, results from a large placebo-controlledrandomized trial in patients with advanced NSCLC who progressed while receiving or within 90 daysof the last dose of chemotherapy or were intolerant to the most recent prior chemotherapy regimen, didnot show an improvement in survival (see CLINICAL PHARMACOLOGY- Clinical Studiessection).Results from two large, controlled, randomized trials in first-line treatment of non-small cell lungcancer showed no benefit from adding IRESSA to doublet, platinum-based chemotherapy.
DrugBank Targets:13 1. Epidermal growth factor receptor
Mechanism of Action:15 
Target: EGFR tyrosine kinase and other tyrosine kinases
Action: inhibitor
FDA: The mechanism of the clinical antitumor action of gefitinib is not fully characterized. Gefitinibinhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembranecell surface receptors, including the tyrosine kinases associated with the epidermal growth factorreceptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells.No clinical studies have been performed that demonstrate a correlation between EGFR receptorexpression and response to gefitinib.
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Istodax15 41 ROMIDEPSIN Gloucester Pharmaceuticals November 2009
FDA Label: Istodax
Disease/s that Drug Treats:cutaneous T-cell lymphoma
Indications and Usage:15 ISTODAX is a histone deacetylase (HDAC) inhibitor indicated for: Treatment of cutaneous T-cell lymphoma (CTCL) in patients who havereceived at least one prior systemic therapy (1). Treatment of peripheral T-cell lymphoma (PTCL) in patients who havereceived at least one prior therapy (1).These indications are based on response rate. Clinical benefit such asimprovement in overall survival has not been demonstrated (1).
DrugBank Targets:13 -
Mechanism of Action:15 
Target: histone deacetylase (HDAC)
Action: inhibitor
FDA: Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in themodulation of gene expression. HDACs also deacetylate non-histone proteins, such as transcription factors. In vitro, romidepsin causes the accumulation of acetylatedhistones, and induces cell cycle arrest and apoptosis of some cancer cell lines with IC50 values in the nanomolar range. The mechanism of the antineoplastic effect ofromidepsin observed in nonclinical and clinical studies has not been fully characterized.
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Ixempra15 41 IXABEPILONE Bristol-Myers Squibb October 2007
FDA Label: Ixempra
Disease/s that Drug Treats:Breast cancer
Indications and Usage:15 IXEMPRA, a microtubule inhibitor, in combination with capecitabine isindicated for the treatment of metastatic or locally advanced breastcancer in patients after failure of an anthracycline and a taxane (1). IXEMPRA as monotherapy is indicated for the treatment of metastaticor locally advanced breast cancer in patients after failure of ananthracycline, a taxane, and capecitabine (1).
DrugBank Targets:13 1. Tubulin beta-3 chain
Mechanism of Action:15 
Target: β-tubulin subunits on microtubules
Action: suppressor of dynamics
FDA: Ixabepilone is a semi-synthetic analog of epothilone B. Ixabepilone binds directlyto β-tubulin subunits on microtubules, leading to suppression of microtubule dynamics.Ixabepilone suppresses the dynamic instability of αβ-II and αβ-III microtubules.Ixabepilone possesses low in vitro susceptibility to multiple tumor resistance mechanisms including efflux transporters, such as MRP-1 and P-glycoprotein (P-gp). Ixabepiloneblocks cells in the mitotic phase of the cell division cycle, leading to cell death.
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Jevtana15 41 CABAZITAXEL sanofi aventis June 2010
FDA Label: Jevtana
Disease/s that Drug Treats:prostate cancer
Indications and Usage:15 JEVTANA is a microtubule inhibitor indicated in combination withprednisone for treatment of patients with hormone-refractory metastaticprostate cancer previously treated with a docetaxel-containing treatmentregimen. (1)
DrugBank Targets:13 1. Tubulin alpha-4A chain;2. Tubulin beta-1 chain
Mechanism of Action:15 
Target: microtubule
Action: inhibitor
FDA: Cabazitaxel is a microtubule inhibitor. Cabazitaxel binds to tubulin and promotes its assemblyinto microtubules while simultaneously inhibiting disassembly. This leads to the stabilization ofmicrotubules, which results in the inhibition of mitotic and interphase cellular functions.
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Kadcyla15 41 ADO-TRASTUZUMAB EMTANSINE Genentech February 2013
FDA Label: Kadcyla
Disease/s that Drug Treats:HER2-positive metastatic breast cancer
Indications and Usage:15 KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugateindicated, as a single agent, for the treatment of patients with HER2-positive,metastatic breast cancer who previously received trastuzumab and a taxane,separately or in combination. Patients should have either: Received prior therapy for metastatic disease, or Developed disease recurrence during or within six months ofcompleting adjuvant therapy. (1)
DrugBank Targets:13 1. Receptor tyrosine-protein kinase erbB-2
Mechanism of Action:15 
Target: microtubule
Action: inhibitor
FDA: Ado-trastuzumab emtansine is a HER2-targeted antibody-drug conjugate. The antibody is thehumanized anti-HER2 IgG1, trastuzumab. The small molecule cytotoxin, DM1, is a microtubuleinhibitor. Upon binding to sub-domain IV of the HER2 receptor, ado-trastuzumab emtansineundergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting inintracellular release of DM1-containing cytotoxic catabolites. Binding of DM1 to tubulindisrupts microtubule networks in the cell, which results in cell cycle arrest and apoptotic celldeath. In addition, in vitro studies have shown that similar to trastuzumab, ado-trastuzumabemtansine inhibits HER2 receptor signaling, mediates antibody-dependent cell-mediatedcytotoxicity and inhibits shedding of the HER2 extracellular domain in human breast cancer cellsthat overexpress HER2.
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Keytruda15 41 PEMBROLIZUMAB Merck September 2014
FDA Label: Keytruda
Disease/s that Drug Treats:unresectable or metastatic melanoma
Indications and Usage:15 KEYTRUDA is a human programmed death receptor-1 (PD-1)-blockingantibody indicated for the treatment of patients with unresectable ormetastatic melanoma and disease progression following ipilimumaband, if BRAF V600 mutation positive, a BRAF inhibitor.This indication is approved under accelerated approval based on tumorresponse rate and durability of response. An improvement in survivalor disease-related symptoms has not yet been established. Continuedapproval for this indication may be contingent upon verification anddescription of clinical benefit in the confirmatory trials. (1)
DrugBank Targets:13 1. Programmed cell death protein 1
Mechanism of Action:15 
Target: PD-1 receptor
Action: blocks interaction withPD-L1 and PD-L2
FDA: Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cellproliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction withPD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including theanti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted indecreased tumor growth.
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Kyprolis15 41 CARFILZOMIB Onyx Pharmaceuticals July 2012
FDA Label: Kyprolis
Disease/s that Drug Treats:multiple myeloma
Indications and Usage:15 Kyprolis is a proteasome inhibitor that is indicated in combination with lenalidomide and dexamethasone for the treatment ofpatients with relapsed multiple myeloma who have received one to threeprior lines of therapy . (1, 14) as a single agent for the treatment of patients with multiple myeloma whohave received at least two prior therapies including bortezomib and animmunomodulatory agent and have demonstrated disease progression on orwithin 60 days of completion of the last therapy. Approval is based onresponse rate. Clinical benefit, such as improvement in survival orsymptoms, has not been verified. (1, 14)
DrugBank Targets:13 1. Proteasome subunit beta type-5;2. Proteasome subunit beta type-8;3. Proteasome subunit beta type-1;4. Proteasome subunit beta type-9;5. Proteasome subunit beta type-2;6. Proteasome subunit beta type-10
Mechanism of Action:15 
Target: tetrapeptide epoxyketone proteasome
Action: inhibitor
FDA: Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds to theN-terminal threonine-containing active sites of the 20S proteasome, the proteolytic coreparticle within the 26S proteasome. Carfilzomib had antiproliferative and proapoptoticactivities in vitro in solid and hematologic tumor cells. In animals, carfilzomib inhibitedproteasome activity in blood and tissue and delayed tumor growth in models of multiplemyeloma, hematologic, and solid tumors.
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Lazanda15 FENTANYL CITRATE Archimedes June 2011
FDA Label: Lazanda
Disease/s that Drug Treats:breakthrough cancer pain
Indications and Usage:15 Lazanda is an opioid agonist indicated for the management of breakthrough painin cancer patients 18 years of age and older who are already receiving and whoare tolerant to opioid therapy for their underlying persistent cancer pain. (1)Limitations of Use:Lazanda may be dispensed only to patients enrolled in the TIRF REMSAccess program.
DrugBank Targets:13 1. Mu-type opioid receptor;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:15 
Target: opiod receptor
Action: agonist
FDA: Fentanyl is a pure opioid agonist whose principal therapeutic action is analgesia. Other members of the class known as opioidagonists include substances such as morphine, oxycodone, hydromorphone, codeine, and hydrocodone.
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Lenvima15 41 LENVATINIB MESYLATE Eisai February 2015
FDA Label: Lenvima
Disease/s that Drug Treats:thyroid cancer
Indications and Usage:15 LENVIMA is a kinase inhibitor indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (1).
DrugBank Targets:13 1. Vascular endothelial growth factor receptor 1;2. Vascular endothelial growth factor receptor 2;3. Vascular endothelial growth factor receptor 3;4. Fibroblast growth factor receptor 1;5. Fibroblast growth factor receptor 2;6. Fibroblast growth factor receptor 3;7. Fibroblast growth factor receptor 4;8. Platelet derived growth factor receptor alpha;9. RET;10. Mast/stem cell growth factor receptor Kit
Mechanism of Action:15 
Target: kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4)
Action: inhibitor
FDA: Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities ofvascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR),and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated inpathogenic angiogenesis, tumor growth, and cancer progression in addition to their normalcellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; theplatelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.
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Leukine15 SARGRAMOSTIM Immunex on November 24, 1995/ November 1996
FDA Label: -
Disease/s that Drug Treats:transplantation/ replenishment of white blood cells, fungal infections
Indications and Usage:15 -
DrugBank Targets:13 1. Granulocyte-macrophage colony-stimulating factor receptor subunit alpha;2. Interleukin-3 receptor subunit alpha;3. Cytokine receptor common subunit beta;4. Syndecan-2;5. Bone marrow proteoglycan
Mechanism of Action:15 
Target: -
Action: -
FDA: -
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Lynparza15 41 OLAPARIB AstraZeneca December 2014
FDA Label: Lynparza
Disease/s that Drug Treats:previously treated BRCA mutated advanced ovarian cancer
Indications and Usage:15 Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated asmonotherapy in patients with deleterious or suspected deleterious germlineBRCA mutated (as detected by an FDA-approved test) advanced ovariancancer who have been treated with three or more prior lines of chemotherapy.(1.1)The indication is approved under accelerated approval based on objectiveresponse rate and duration of response. Continued approval for this indicationmay be contingent upon verification and description of clinical benefit inconfirmatory trials. (1 1, 14)
DrugBank Targets:13 1. Poly [ADP-ribose] polymerase 1;2. Poly [ADP-ribose] polymerase 2;3. Poly [ADP-ribose] polymerase 3
Mechanism of Action:15 
Target: poly (ADP-ribose) polymerase (PARP)
Action: inhibitor
FDA: Lynparza is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3.PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNArepair. Olaparib has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mousexenograft models of human cancer both as monotherapy or following platinum-based chemotherapy. Increasedcytotoxicity and anti-tumor activity following treatment with olaparib were noted in cell lines and mouse tumor modelswith deficiencies in BRCA. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition ofPARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasisand cell death.
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Marqibo15 41 VINCRISTINE SULFATE Talon Therapeutics August 2012
FDA Label: Marqibo
Disease/s that Drug Treats:Ph- acute lymphoblastic leukemia
Indications and Usage:15 Marqibo is a vinca alkaloid indicated for the treatment of adult patients withPhiladelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL)in second or greater relapse or whose disease has progressed following two ormore anti-leukemia therapies. This indication is based on overall responserate. Clinical benefit such as improvement in overall survival has not beenverified (1.1).
DrugBank Targets:13 1. Tubulin beta chain;2. Tubulin alpha-4A chain
Mechanism of Action:15 
Target: tubulin
Action: alters polymerization equilibrium
FDA: Marqibo is a sphingomyelin/cholesterol liposome-encapsulated formulation of vincristine sulfate.Non-liposomal vincristine sulfate binds to tubulin, altering the tubulin polymerization equilibrium, resulting inaltered microtubule structure and function. Non-liposomal vincristine sulfate stabilizes the spindle apparatus,preventing chromosome segregation, triggering metaphase arrest and inhibition of mitosis.
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Mekinist15 41 TRAMETINIB DIMETHYL SULFOXIDE GlaxoSmithKline May of 2013
FDA Label: Mekinist
Disease/s that Drug Treats:unresectable or metastatic melanoma with BRAF V600E or V600K mutations
Indications and Usage:15 MEKINIST is a kinase inhibitor indicated as a single agent and incombination with dabrafenib for the treatment of patients with unresectable ormetastatic melanoma with BRAF V600E or V600K mutations as detected byan FDA-approved test. The use in combination is based on the demonstrationof durable response rate. Improvement in disease-related symptoms or overallsurvival has not been demonstrated for MEKINIST in combination withdabrafenib. (1, 14.1)Limitation of use: MEKINIST as a single agent is not indicated for treatmentof patients who have received prior BRAF-inhibitor therapy. (1)
DrugBank Targets:13 1. Dual specificity mitogen-activated protein kinase kinase 1;2. Dual specificity mitogen-activated protein kinase kinase 2
Mechanism of Action:15 
Target: mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activation and of MEK1 and MEK2 kinase
Action: inhibitor
FDA: Trametinib is a reversible inhibitor of mitogen-activated extracellular signal-regulated kinase 1(MEK1) and MEK2 activation and of MEK1 and MEK2 kinase activity. MEK proteins areupstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotescellular proliferation. BRAF V600E mutations result in constitutive activation of the BRAFpathway which includes MEK1 and MEK2. Trametinib inhibits BRAF V600 mutation-positivemelanoma cell growth in vitro and in vivo.Trametinib and dabrafenib target two different tyrosine kinases in the RAS/RAF/MEK/ERKpathway. Use of trametinib and dabrafenib in combination resulted in greater growth inhibitionof BRAF V600 mutation-positive melanoma cell lines in vitro and prolonged inhibition of tumorgrowth in BRAF V600 mutation positive melanoma xenografts compared with either drug alone.
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Neumega15 OPRELVEKIN Genetics Institute November 1997
FDA Label: Neumega
Disease/s that Drug Treats:platelet deficiency
Indications and Usage:15 Neumega is indicated for the prevention of severe thrombocytopenia and the reduction of theneed for platelet transfusions following myelosuppressive chemotherapy in adult patients withnonmyeloid malignancies who are at high risk of severe thrombocytopenia. Efficacy wasdemonstrated in patients who had experienced severe thrombocytopenia following the previouschemotherapy cycle. Neumega is not indicated following myeloablative chemotherapy (seeWARNINGS, Increased Toxicity Following Myeloablative Therapy). The safety andeffectiveness of Neumega have not been established in pediatric patients.
DrugBank Targets:13 1. Interleukin-11 receptor subunit alpha
Mechanism of Action:15 
Target: bone-forming and bone-resorbing cells (additionally other non-hematopoietic activities)
Action: stimulator of megakaryocytopoiesis andthrombopoiesis
FDA: The primary hematopoietic activity of Neumega is stimulation of megakaryocytopoiesis andthrombopoiesis. Neumega has shown potent thrombopoietic activity in animal models ofcompromised hematopoiesis, including moderately to severely myelosuppressed mice andnonhuman primates. In these models, Neumega improved platelet nadirs and accelerated plateletrecoveries compared to controls.Preclinical trials have shown that mature megakaryocytes which develop during in vivo treatmentwith Neumega are ultrastructurally normal. Platelets produced in response to Neumega weremorphologically and functionally normal and possessed a normal life span.IL-11 has also been shown to have non-hematopoietic activities in animals including theregulation of intestinal epithelium growth (enhanced healing of gastrointestinal lesions), theinhibition of adipogenesis, the induction of acute phase protein synthesis, inhibition of pro-inflammatory cytokine production by macrophages, and the stimulation of osteoclastogenesisand neurogenesis. Non-hematopoietic pathologic changes observed in animals include fibrosis oftendons and joint capsules, periosteal thickening, papilledema, and embryotoxicity (seePRECAUTIONS, Pediatric Use and PRECAUTIONS, Pregnancy Category C).IL-11 is produced by bone marrow stromal cells and is part of the cytokine family that shares thegp130 signal transducer. Primary osteoblasts and mature osteoclasts express mRNAs for both IL-11 receptor (IL-11R alpha) and gp130. Both bone-forming and bone-resorbing cells are potentialtargets of IL-11. (1)
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Neutroval15 tbo-filgrastim Teva Pharmaceutical August 2012
FDA Label: -
Disease/s that Drug Treats:severe chemotherapy-induced neutropenia
Indications and Usage:15 -
DrugBank Targets:13 1. Granulocyte colony-stimulating factor receptor;2. Neutrophil elastase
Mechanism of Action:15 
Target: G-CSF receptors
Action: stimulates proliferation of neutrofils
FDA: -
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Nexavar15 41 SORAFENIB TOSYLATE Bayer/Onyx December 2005
FDA Label: Nexavar
Disease/s that Drug Treats:Renal Cell Carcinoma
Indications and Usage:15 NEXAVAR is a kinase inhibitor indicated for the treatment of Unresecta ble hepatocellular carcinoma (1.1) adjust thyroid repla cement therapy in patients with thyroid ca ncer. (5.12) Advanced renal cell carcinoma (1.2) Locally recurrent or meta static, progressive, differentiated thyroid carcinoma refractory to ra dioactive iodine treatment (1.3)
DrugBank Targets:13 1. Serine/threonine-protein kinase B-raf;2. RAF proto-oncogene serine/threonine-protein kinase;3. Vascular endothelial growth factor receptor 3;4. Vascular endothelial growth factor receptor 2;5. Receptor-type tyrosine-protein kinase FLT3;6. Platelet-derived growth factor receptor beta;7. Mast/stem cell growth factor receptor Kit;8. Fibroblast growth factor receptor 1;9. Proto-oncogene tyrosine-protein kinase receptor Ret;10. Vascular endothelial growth factor receptor 1
Mechanism of Action:15 
Target: c-CRAF, BRAF and mutant BRAF, KIT, FLT- 3, RET, RET/PTC, VEGFR-1, VEGFR- 2, VEGFR- 3, and PDGFR-ß
Action: inhibitor
FDA: Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro.Sorafenib was shown to inhibit multiple intracellular (c-CRAF, BRAF and mutant BRAF) and cell surfacekinases (KIT, FLT- 3, RET, RET/PTC, VEGFR-1, VEGFR- 2, VEGFR- 3, and PDGFR-ß). Several of thesekinases are thought to be involved in tumor cell signaling, angiogenesis and apoptosis. Sorafenib inhibited tumorgrowth of HCC, RCC, and DTC human tumor xenografts in immunocompromised mice. Reductions in tumorangiogenesis were seen in models of HCC and RCC upon sorafenib treatment, and increases in tumor apoptosiswer e obser ved in models of HCC, RCC, and DTC.
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Nolvadex15 41 TAMOXIFEN CITRATE AstraZeneca October 1998
FDA Label: Nolvadex
Disease/s that Drug Treats:Breast Cancer
Indications and Usage:15 Metastatic Breast Cancer:NOLVADEX is effective in the treatment of metastatic breast cancer in women and men. Inpremenopausal women with metastatic breast cancer, NOLVADEX is an alternative tooophorectomy or ovarian irradiation. Available evidence indicates that patients whose tumorsare estrogen receptor positive are more likely to benefit from NOLVADEX therapy.Adjuvant Treatment of Breast Cancer:NOLVADEX is indicated for the treatment of node-positive breast cancer in women followingtotal mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. In someNOLVADEX adjuvant studies, most of the benefit to date has been in the subgroup with four ormore positive axillary nodes.NOLVADEX is indicated for the treatment of axillary node-negative breast cancer in womenfollowing total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation.The estrogen and progesterone receptor values may help to predict whether adjuvantNOLVADEX therapy is likely to be beneficial.NOLVADEX reduces the occurrence of contralateral breast cancer in patients receiving adjuvantNOLVADEX therapy for breast cancer.Ductal Carcinoma in Situ (DCIS):In women with DCIS, following breast surgery and radiation, NOLVADEX is indicated toreduce the risk of invasive breast cancer (see BOXED WARNING at the beginning of thelabel). The decision regarding therapy with NOLVADEX for the reduction in breast cancerincidence should be based upon an individual assessment of the benefits and risks ofNOLVADEX therapy.Current data from clinical trials support five years of adjuvant NOLVADEX therapy for patientswith breast cancer. Reduction in Breast Cancer Incidence in High Risk Women:NOLVADEX is indicated to reduce the incidence of breast cancer in women at high risk forbreast cancer. This effect was shown in a study of 5 years planned duration with a medianfollow-up of 4.2 years. Twenty-five percent of the participants received drug for 5 years. Thelonger-term effects are not known. In this study, there was no impact of tamoxifen on overall orbreast cancer-related mortality (see BOXED WARNING at the beginning of the label).NOLVADEX is indicated only for high-risk women. “High risk” is defined as women at least35 years of age with a 5-year predicted risk of breast cancer ≥ 1.67%, as calculated by the GailModel.Examples of combinations of factors predicting a 5-year risk ≥ 1.67% are:Age 35 or older and any of the following combination of factors: One first degree relative with a history of breast cancer, 2 or more benign biopsies, and ahistory of a breast biopsy showing atypical hyperplasia; or At least 2 first degree relatives with a history of breast cancer, and a personal history of atleast one breast biopsy; or LCISAge 40 or older and any of the following combination of factors: One first degree relative with a history of breast cancer, 2 or more benign biopsies, age at firstlive birth 25 or older, and age at menarche 11 or younger; or At least 2 first degree relatives with a history of breast cancer, and age at first live birth 19 oryounger; or One first degree relative with a history of breast cancer, and a personal history of a breastbiopsy showing atypical hyperplasia.Age 45 or older and any of the following combination of factors: At least 2 first degree relatives with a history of breast cancer and age at first live birth 24 oryounger; or One first degree relative with a history of breast cancer with a personal history of a benignbreast biopsy, age at menarche 11 or less and age at first live birth 20 or more.Age 50 or older and any of the following combination of factors: At least 2 first degree relatives with a history of breast cancer; or History of one breast biopsy showing atypical hyperplasia, and age at first live birth 30 orolder and age at menarche 11 or less; or History of at least two breast biopsies with a history of atypical hyperplasia, and age at firstlive birth 30 or more.Age 55 or older and any of the following combination of factors: One first degree relative with a history of breast cancer with a personal history of a benignbreast biopsy, and age at menarche 11 or less; or History of at least 2 breast biopsies with a history of atypical hyperplasia, and age at first livebirth 20 or older.Age 60 or older and: 5-year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model.For women whose risk factors are not described in the above examples, the Gail Model isnecessary to estimate absolute breast cancer risk. Health Care Professionals can obtain a GailModel Risk Assessment Tool by dialing 1-800-544-2007.There are insufficient data available regarding the effect of NOLVADEX on breast cancerincidence in women with inherited mutations (BRCA1, BRCA2) to be able to make specificrecommendations on the effectiveness of NOLVADEX in these patients.After an assessment of the risk of developing breast cancer, the decision regarding therapy withNOLVADEX for the reduction in breast cancer incidence should be based upon an individualassessment of the benefits and risks of NOLVADEX therapy. In the NSABP P-1 trial,NOLVADEX treatment lowered the risk of developing breast cancer during the follow-up periodof the trial, but did not eliminate breast cancer risk (See Table 3 in CLINICALPHARMACOLOGY).
DrugBank Targets:13 1. Estrogen receptor;2. Estrogen receptor beta;3. 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase;4. Protein kinase C
Mechanism of Action:15 
Target: estrogen receptors
Action: competitor with estraidiol
FDA: NOLVADEX is a nonsteroidal agent that has demonstrated potent antiestrogenic properties inanimal test systems. The antiestrogenic effects may be related to its ability to compete withestrogen for binding sites in target tissues such as breast. Tamoxifen inhibits the induction of ratmammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression ofalready established DMBA-induced tumors. In this rat model, tamoxifen appears to exert itsantitumor effects by binding the estrogen receptors.In cytosols derived from human breast adenocarcinomas, tamoxifen competes with estradiol forestrogen receptor protein.
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Odomzo15 41 SONIDEGIB PHOSPHATE Novartis Jul-15
FDA Label: Odomzo
Disease/s that Drug Treats:locally advanced basal cell carcinoma
Indications and Usage:15 ODOMZO is a hedgehog pathway inhibitor indicated for the treatment ofadult patients with locally advanced basal cell carcinoma (BCC) that hasrecurred following surgery or radiation therapy, or those who are notcandidates for surgery or radiation therapy. (1)
DrugBank Targets: -
Mechanism of Action:15 
Target: Smoothened
Action: inhibitor
FDA: Sonidegib is an inhibitor of the Hedgehog pathway. Sonidegib binds to and inhibits Smoothened, a transmembrane proteininvolved in Hedgehog signal transduction.
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Onsolis15 FENTANYL CITRATE BioDelivery Sciences July 2009
FDA Label: Onsolis
Disease/s that Drug Treats:breakthrough cancer pain
Indications and Usage:15 Onsolis is an opioid agonist indicated for the management of breakthrough painin cancer patients 18 years of age and older who are already receiving and whoare tolerant to opioid therapy for their underlying persistent cancer pain. (1)Limitations of Use:Onsolis may be dispensed only to patients enrolled in the TIRF REMS Accessprogram.
DrugBank Targets:13 1. Mu-type opioid receptor;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:15 
Target: mu-opioid receptor
Action: agonist
FDA: Fentanyl is a pure opioid agonist whose principal therapeutic action is analgesia. Other members of the class known asopioid agonists include substances such as morphine, oxycodone, hydromorphone, codeine, and hydrocodone.
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Opdivo15 41 NIVOLUMAB Bristol-Myers Squibb March 2015/ December 2014
FDA Label: Opdivo
Disease/s that Drug Treats:metastatic squamous non-small cell lung cancer/ unresectable or metastatic melanoma
Indications and Usage:15 OPDIVO is a programmed death receptor-1 (PD-1) blocking antibodyindicated for the treatment of patients with: unresectable or metastatic melanoma and disease progression followingipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. (1.1)This indication is approved under accelerated approval based on tumorresponse rate and durability of response. Continued approval for thisindication may be contingent upon verification and description of clinicalbenefit in the confirmatory trials. (1.1, 14.1) metastatic squamous non-small cell lung cancer with progression on orafter platinum-based chemotherapy. (1.2)
DrugBank Targets:13 1. Programmed cell death protein 1
Mechanism of Action:15 
Target: PD-1 receptor
Action: blocker of interaction with PD-L1 and PD-L2
FDA: Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibitsT-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in sometumors and signaling through this pathway can contribute to inhibition of active T-cell immunesurveillance of tumors. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibodythat binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1pathway-mediated inhibition of the immune response, including the anti-tumor immuneresponse. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumorgrowth.
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Perjeta15 41 PERTUZUMAB Genentech June 2012
FDA Label: Perjeta
Disease/s that Drug Treats:HER2+ metastatic breast cancer
Indications and Usage:15 PERJETA is a HER2/neu receptor antagonist indicated for: Use in combination with trastuzumab and docetaxel for treatment ofpatients with HER2-positive metastatic breast cancer (MBC) who havenot received prior anti-HER2 therapy or chemotherapy for metastaticdisease. (1.1) Use in combination with trastuzumab and docetaxel as neoadjuvanttreatment of patients with HER2-positive, locally advanced,inflammatory, or early stage breast cancer (either greater than 2 cm indiameter or node positive) as part of a complete treatment regimen forearly breast cancer. This indication is based on demonstration of animprovement in pathological complete response rate. No data areavailable demonstrating improvement in event-free survival or overallsurvival. (1.2, 2.1, 14.2)Limitations of Use: The safety of PERJETA as part of a doxorubicin-containing regimenhas not been established. The safety of PERJETA administered for greater than 6 cycles forearly breast cancer has not been established.
DrugBank Targets:13 1. Receptor tyrosine-protein kinase erbB-2
Mechanism of Action:15 
Target: mitogen-activated protein (MAP) kinase, phosphoinositide 3-kinase445 (PI3K)
Action: inhibitor of ligand-initiated intracellular signaling
FDA: Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3, and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein (MAP) kinase, and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity (ADCC). While pertuzumab alone inhibited the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab augmented anti-tumor activity in HER2-overexpressing xenograft models.
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Photofrin15 PORFIMER SODIUM QLT January 1998
FDA Label: Photofrin
Disease/s that Drug Treats:Non-small cell lung cancer
Indications and Usage:15 PHOTOFRIN is a photodynamic therapy drug indicated for:Esophageal Cancer (1.1) Palliation of patients with completely obstructing esophageal cancer, or ofpatients with partially obstructing esophageal cancer who, in the opinion oftheir physician, cannot be satisfactorily treated with Nd:YAG laser therapyEndobronchial Cancer (1.2) Treatment of microinvasive endobronchial non-small-cell lung cancer(NSCLC) in patients for whom surgery and radiotherapy are not indicated Reduction of obstruction and palliation of symptoms in patients withcompletely or partially obstructing endobronchial NSCLCHigh-Grade Dysplasia in Barrett’s Esophagus (1.3) Ablation of high-grade dysplasia (HGD) in Barrett’s esophagus (BE)patients who do not undergo esophagectomy
DrugBank Targets:13 1. Low-density lipoprotein receptor;2. High affinity immunoglobulin gamma Fc receptor I
Mechanism of Action:15 
Target: tumor cells
Action: prpagates radical reactions
FDA: Cellular damage caused by photodynamic therapy (PDT) withPHOTOFRIN is a consequence of the propagation of radical reactions.Radical initiation may occur after porfimer sodium absorbs light to forma porphyrin excited state. Spin transfer from porfimer sodium tomolecular oxygen may then generate singlet oxygen. Subsequentradical reactions can form superoxide and hydroxyl radicals. Tumordeath also occurs through ischemic necrosis secondary to vascularocclusion that appears to be partly mediated by thromboxane A2 release.As opposed to a thermal effect, the laser treatment with porfimersodium induces a photochemical effect. The necrotic reaction andassociated inflammatory responses may evolve over several days.
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Picato gel15 INGENOL MEBUTATE LEO Pharma January 2012
FDA Label: Picato gel
Disease/s that Drug Treats:actinic keratosis
Indications and Usage:15 Picato® gel is an inducer of cell death indicated for the topical treatment ofactinic keratosis. (1)
DrugBank Targets:13 1. Protein kinase C delta type;2. Protein kinase C alpha type
Mechanism of Action:15 
Target: AK lesions
Action: inducer of apoptosis (otherwise, mechanism of action is unknown)
FDA: The mechanism of action by which Picato® gel induces cell death in treating AK lesions isunknown.
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Plenaxis15 ABARELIX Praecis Pharmaceuticals December 2003
FDA Label: Plenaxis
Disease/s that Drug Treats:Prostate Cancer
Indications and Usage:15 Plenaxis™ is indicated for the palliative treatment of men with advanced symptomaticprostate cancer, in whom LHRH agonist therapy is not appropriate and who refusesurgical castration, and have one or more of the following: (1) risk of neurologicalcompromise due to metastases, (2) ureteral or bladder outlet obstruction due to localencroachment or metastatic disease, or (3) severe bone pain from skeletal metastasespersisting on narcotic analgesia.
DrugBank Targets:13 1. Gonadotropin-releasing hormone receptor
Mechanism of Action:15 
Target: GnRH receptors in the pituitary gland
Action: competitive blocker
FDA: -
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Pomalyst15 41 POMALIDOMIDE Celgene February 2013
FDA Label: Pomalyst
Disease/s that Drug Treats:relapsed and refractory multiple myeloma
Indications and Usage:15 POMALYST is a thalidomide analogue indicated, in combination withdexamethasone, for patients with multiple myeloma who have received atleast two prior therapies including lenalidomide and a proteasome inhibitorand have demonstrated disease progression on or within 60 days ofcompletion of the last therapy (1.1).
DrugBank Targets:13 1. Protein cereblon;2. Tumor necrosis factor;3. Prostaglandin G/H synthase 2
Mechanism of Action:15 
Target: hematopoietic tumor cells, lenalidomide-resistant multiple myeloma cell lines/ T-cells
Action: inhibitor of proliferation/ inducer of apoptosis/ enhancer of natural killer cell-mediated immunity
FDA: Pomalidomide, an analogue of thalidomide, is an immunomodulatory agent with antineoplasticactivity. In in vitro cellular assays, pomalidomide inhibited proliferation and induced apoptosis of hematopoietic tumor cells. Additionally, pomalidomide inhibited the proliferation oflenalidomide-resistant multiple myeloma cell lines and synergized with dexamethasone in bothlenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumor cell apoptosis.Pomalidomide enhanced T cell- and natural killer (NK) cell-mediated immunity and inhibitedproduction of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. Pomalidomidedemonstrated anti-angiogenic activity in a mouse tumor model and in the in vitro umbilical cordmodel.
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Premarin15 ESTROGENS CONJUGATED Wyeth July of 2003
FDA Label: Premarin
Disease/s that Drug Treats:prevention of postmenopausal osteoporosis and treatment of vasomotor menopause symptoms
Indications and Usage:15 PREMARIN is a mixture of estrogens indicated for: Treatment of Moderate to Severe Vasomotor Symptoms due toMenopause (1.1) Treatment of Moderate to Severe Vulvar and Vaginal Atrophy due toMenopause (1.2) Treatment of Hypoestrogenism due to Hypogonadism, Castration orPrimary Ovarian Failure (1.3) Treatment of Breast Cancer (for Palliation Only) in AppropriatelySelected Women and Men with Metastatic Disease (1.4) Treatment of Advanced Androgen-Dependent Carcinoma of theProstate (for Palliation Only) (1.5) Prevention of Postmenopausal Osteoporosis (1.6)
DrugBank Targets:13 1. Estrogen receptor
Mechanism of Action:15 
Target: nuclear receptors in estrogen-responsive tissues
Action: reduce theelevated levels of gonadotropins
FDA: Endogenous estrogens are largely responsible for the development and maintenance of thefemale reproductive system and secondary sexual characteristics. Although circulatingestrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is theprincipal intracellular human estrogen and is substantially more potent than its metabolites,estrone and estriol, at the receptor level.The primary source of estrogen in normally cycling adult women is the ovarian follicle, whichsecretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.After menopause, most endogenous estrogen is produced by conversion of androstenedione,secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and thesulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens inpostmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date,two estrogen receptors have been identified. These vary in proportion from tissue to tissue.Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizinghormone (LH) and FSH, through a negative feedback mechanism. Estrogens act to reduce theelevated levels of these gonadotropins seen in postmenopausal women.
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Proleukin15 41 ALDESLEUKIN Chiron January 1998
FDA Label: Proleukin
Disease/s that Drug Treats:Metastatic melanoma
Indications and Usage:15 Proleukin® (aldesleukin) is indicated for the treatment of adults with metastatic renal cellcarcinoma (metastatic RCC).Proleukin is indicated for the treatment of adults with metastatic melanoma.Careful patient selection is mandatory prior to the administration of Proleukin. See“CONTRAINDICATIONS”, “WARNINGS” and “PRECAUTIONS” sections regarding patientscreening, including recommended cardiac and pulmonary function tests and laboratorytests.Evaluation of clinical studies to date reveals that patients with more favorable ECOGperformance status (ECOG PS 0) at treatment initiation respond better to Proleukin, with ahigher response rate and lower toxicity (See “CLINICAL PHARMACOLOGY” section,“CLINICAL STUDIES” section and “ADVERSE REACTIONS” section). Therefore, selectionof patients for treatment should include assessment of performance status.Experience in patients with ECOG PS >1 is extremely limited.
DrugBank Targets:13 1. Interleukin-2 receptor subunit beta;2. Interleukin-2 receptor subunit alpha;3. Cytokine receptor common subunit gamma
Mechanism of Action:15 
Target: human cells
Action: enhancer of immune response and strnaght ( lymphocytemitogenesis, growth of human interleukin-2 dependent cell lines, lymphocyte cytotoxicity, induction of killer cell activity and interferon-gamma production)
FDA: Proleukin® (aldesleukin) has been shown to possess the biological activities of human nativeinterleukin-2.1,2 In vitro studies performed on human cell lines demonstrate theimmunoregulatory properties of Proleukin, including: a) enhancement of lymphocytemitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines;b) enhancement of lymphocyte cytotoxicity; c) induction of killer cell (lymphokine-activated(LAK) and natural (NK)) activity; and d) induction of interferon-gamma production.The in vivo administration of Proleukin in animals and humans produces multipleimmunological effects in a dose dependent manner. These effects include activation ofcellular immunity with profound lymphocytosis, eosinophilia, and thrombocytopenia, and theproduction of cytokines including tumor necrosis factor, IL-1 and gamma interferon. 3 In vivoexperiments in murine tumor models have shown inhibition of tumor growth.4 The exactmechanism by which Proleukin mediates its antitumor activity in animals and humans isunknown.
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Provenge15 41 sipuleucel-T Dendreon May 2010
FDA Label: Provenge
Disease/s that Drug Treats:hormone refractory prostate cancer
Indications and Usage:15 PROVENGE is an autologous cellularimmunotherapy indicated for the treatment ofasymptomatic or minimally symptomatic metastaticcastrate resistant (hormone refractory) prostatecancer. (1)
DrugBank Targets: -
Mechanism of Action:15 
Target: PAP
Action: inducer of immune response against this antigen expressed in most prostate cancers
FDA: PROVENGE is classified as an autologous cellular immunotherapy. While the precisemechanism of action is unknown, PROVENGE is designed to induce an immune responsetargeted against PAP, an antigen expressed in most prostate cancers. During ex vivo culturewith PAP-GM-CSF, APCs take up and process the recombinant target antigen into smallpeptides that are then displayed on the APC surface.In Study 1, 237 out of the 512 patients randomized were evaluated for the development ofhumoral and T cell immune responses (proliferative and gamma-interferon (γIFN) ELISPOT)to the target antigens at Baseline, and at Weeks 6, 14, and 26. Antibody (IgM and IgG)responses against PAP-GM-CSF and PAP antigen alone were observed through thefollow-up period in the PROVENGE group. Neutralizing antibody responses to GM-CSFwere transient. T cell proliferative and γIFN ELISPOT responses to PAP-GM-CSF fusionprotein were observed in cells collected from peripheral blood of patients through thefollow-up period in the PROVENGE treatment group but not in controls. In some patients aresponse to PAP antigen alone was observed. No conclusions could be made regarding theclinical significance of the observed immune responses.
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Revlimid15 41 LENALIDOMIDE Celgene June 2013
FDA Label: Revlimid
Disease/s that Drug Treats:mantle cell lymphoma
Indications and Usage:15 REVLIMID is a thalidomide analogue indicated for the treatment of patientswith: Multiple myeloma (MM), in combination with dexamethasone (1.1). Transfusion-dependent anemia due to low- or intermediate-1-riskmyelodysplastic syndromes (MDS) associated with a deletion 5qabnormality with or without additional cytogenetic abnormalities (1.2). Mantle cell lymphoma (MCL) whose disease has relapsed or progressedafter two prior therapies, one of which included bortezomib (1.3).Limitations of Use: REVLIMID is not indicated and is not recommended for the treatmentof patients with chronic lymphocytic leukemia (CLL) outside ofcontrolled clinical trials (1.4).
DrugBank Targets:13 1. Protein cereblon;2. Tumor necrosis factor ligand superfamily member 11;3. Cadherin-5;4. Prostaglandin G/H synthase 2
Mechanism of Action:15 
Target: T cells and natural killer cells/ pro-inflammatory cytokines by monocytes
Action: activator/inhibitor
FDA: Lenalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. Lenalidomide inhibitsproliferation and induces apoptosis of certain hematopoietic tumor cells including multiple myeloma, mantle cell lymphoma, and del (5q)myelodysplastic syndromes in vitro. Lenalidomide causes a delay in tumor growth in some in vivo nonclinical hematopoietic tumor modelsincluding multiple myeloma. Immunomodulatory properties of lenalidomide include activation of T cells and natural killer (NK) cells, increasednumbers of NKT cells, and inhibition of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. In multiple myeloma cells, thecombination of lenalidomide and dexamethasone synergizes the inhibition of cell proliferation and the induction of apoptosis.
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Rituxan15 41 RITUXIMAB Biogen IDEC, Genentech November 1997
FDA Label: Rituxan
Disease/s that Drug Treats:non-hodgkin's lymphoma
Indications and Usage:15 Rituxan® (rituximab) is a CD20-directed cytolytic antibody indicated for thetreatment of patients with: Non-Hodgkin’s Lymphoma (NHL) (1.1) Chronic Lymphocytic Leukemia (CLL) (1.2) Rheumatoid Arthritis (RA) in combination with methotrexate in adultpatients with moderately-to severely-active RA who have inadequateresponse to one or more TNF antagonist therapies (1.3) Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) andMicroscopic Polyangiitis (MPA) in adult patients in combination withglucocorticoids (1.4)Limitations of Use: Rituxan is not recommended for use in patients withsevere, active infections (1.5).
DrugBank Targets:13 1. Low affinity immunoglobulin gamma Fc region receptor III-B;2. Complement C1r subcomponent;3. Complement C1q subcomponent subunit A;4. Complement C1q subcomponent subunit B;5. Complement C1q subcomponent subunit C;6. Low affinity immunoglobulin gamma Fc region receptor III-A;7. Complement C1s subcomponent;8. High affinity immunoglobulin gamma Fc receptor I;9. Low affinity immunoglobulin gamma Fc region receptor II-a;10. Low affinity immunoglobulin gamma Fc region receptor II-b;11. Low affinity immunoglobulin gamma Fc region receptor II-c;12. B-lymphocyte antigen CD20
Mechanism of Action:15 
Target: CD20 antigen expressed on the surface ofpre-B and mature B-lymphocytes
Action: mediator of B-cell lysis through different possible types of cytotoxicity
FDA: Rituximab is a monoclonal antibody that targets the CD20 antigen expressed on the surface ofpre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possiblemechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependentcell mediated cytotoxicity (ADCC). The antibody induced apoptosis in the DHL 4 human B celllymphoma cell line.B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associatedchronic synovitis. In this setting, B cells may be acting at multiple sites in theautoimmune/inflammatory process, including through production of rheumatoid factor (RF) andother autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokineproduction.
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Sensipar15 CINACALCET HYDROCHLORIDE Amgen March 2004
FDA Label: Sensipar
Disease/s that Drug Treats:Hyperparathyroidism / Hypercalcemia
Indications and Usage:15 Sensipar is a calcium-sensing receptor agonist indicated for: concentration time curve) is increased in patients with moderate and Secondary Hyperparathyroidism (HPT) in adult patients with chronic severe hepatic impairment. Patients should be closely monitored forkidney disease (CKD) on dialysis. (1.1) serum calcium, serum phosphorus, and iPTH levels throughout Hypercalcemia in adult patients with Parathyroid Carcinoma (PC). (1.2) treatment. (5.3, 8.7) Hypercalcemia in adult patients with primary HPT for whomparathyroidectomy would be indicated on the basis of serum calciumlevels, but who are unable to undergo parathyroidectomy. (1.3)
DrugBank Targets:13 1. Extracellular calcium-sensing receptor
Mechanism of Action:15 
Target: calcium-sensing receptor
Action: increases sensitivity to activation by extracellular calcium
FDA: The calcium-sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulatorof PTH synthesis and secretion. Cinacalcet, the active ingredient in Sensipar, directly lowers PTH levels byincreasing the sensitivity of the calcium-sensing receptor to extracellular calcium. The reduction in PTH isassociated with a concomitant decrease in serum calcium levels.
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Sprycel15 41 DASATINIB Bristol-Myers Squibb June 2006
FDA Label: Sprycel
Disease/s that Drug Treats:Chronic Myeloid Leukemia
Indications and Usage:15 SPRYCEL is a kinase inhibitor indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+)chronic myeloid leukemia (CML) in chronic phase. (1, 14) adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+CML with resistance or intolerance to prior therapy including imatinib. (1,14) adults with Philadelphia chromosome-positive acute lymphoblasticleukemia (Ph+ ALL) with resistance or intolerance to prior therapy. (1, 14)
DrugBank Targets:13 1. Tyrosine-protein kinase ABL1;2. Proto-oncogene tyrosine-protein kinase Src;3. Ephrin type-A receptor 2;4. Tyrosine-protein kinase Lck;5. Tyrosine-protein kinase Yes;6. Mast/stem cell growth factor receptor Kit;7. Platelet-derived growth factor receptor beta;8. Signal transducer and activator of transcription 5B;9. Abelson tyrosine-protein kinase 2;10. Tyrosine-protein kinase Fyn
Mechanism of Action:15 
Target: BCR-ABL, SRC family(SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ kinases
Action: inhibitor
FDA: Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family(SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib ispredicted to bind to multiple conformations of the ABL kinase.In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylatesensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia(CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under theconditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCRABLkinase domain mutations, activation of alternate signaling pathways involving the SRCfamily kinases (LYN, HCK), and multi-drug resistance gene overexpression.
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Stivarga15 41 REGORAFENIB Bayer/ Bayer HealthCare Pharmaceuticals February 2013/ September 2012
FDA Label: Stivarga
Disease/s that Drug Treats:gastrointestinal stromal tumor/ metastatic colorectal cancer
Indications and Usage:15 Stivarga is a kinase inhibitor indicated for the treatment of patients with: Metastatic colorectal cancer (CRC) who have been previously treated withfluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an antiVEGFtherapy, and, if KRAS wild type, an anti-EGFR therapy. (1.1) Locally advanced, unresectable or metastatic gastrointestinal stromal tumor(GIST) who have been previously treated with imatinib mesylate andsunitinib malate. (1.2)
DrugBank Targets:13 1. Proto-oncogene tyrosine-protein kinase receptor Ret;2. Vascular endothelial growth factor receptor 1;3. Vascular endothelial growth factor receptor 2;4. Vascular endothelial growth factor receptor 3;5. Mast/stem cell growth factor receptor Kit;6. Platelet-derived growth factor receptor alpha;7. Platelet-derived growth factor receptor beta;8. Fibroblast growth factor receptor 1;9. Fibroblast growth factor receptor 2;10. Angiopoietin-1 receptor;11. Discoidin domain-containing receptor 2;12. High affinity nerve growth factor receptor;13. Ephrin type-A receptor 2;14. RAF proto-oncogene serine/threonine-protein kinase;15. Serine/threonine-protein kinase B-raf;16. Mitogen-activated protein kinase 11;17. Tyrosine-protein kinase FRK;18. Tyrosine-protein kinase ABL1
Mechanism of Action:15 
Target: RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2,TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAFV600E , SAPK2, PTK5, and Abl kinases
Action: inhibitor
FDA: Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normalcellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumormicroenvironment. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 andM-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2,TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAFV600E , SAPK2, PTK5, and Abl at concentrations of regorafenib thathave been achieved clinically. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model,and inhibition of tumor growth as well as anti-metastatic activity in several mouse xenograft models including some forhuman colorectal carcinoma.
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Subsys15 FENTANYL Insys Therapeutics January of 2012
FDA Label: Subsys
Disease/s that Drug Treats:breakthrough cancer pain
Indications and Usage:15 SUBSYS is an opioid agonist indicated for the management of breakthroughpain in cancer patients 18 years of age and older who are already receivingand who are tolerant to opioid therapy for their underlying persistent cancerpain. Patients must remain on around-the-clock opioids when takingSUBSYS. (1)Limitations of Use:SUBSYS may be dispensed only to patients enrolled in the TIRF REMSACCESS program.
DrugBank Targets:13 1. Mu-type opioid receptor;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:15 
Target: opiod receptors?
Action: agonist
FDA: Fentanyl is an opioid agonist whose principal therapeutic action is analgesia.Other members of the class known as opioid agonists include substances such asmorphine, oxycodone, hydromorphone, codeine, and hydrocodone.
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Sutent15 41 SUNITINIB MALATE Pfizer May 2011/ January 2006
FDA Label: Sutent
Disease/s that Drug Treats:pancreatic neuroendocrine tumors/ Kidney Cancer/Gastrointestinal Stromal Tumors
Indications and Usage:15 SUTENT is a kinase inhibitor indicated for the treatment of: Gastrointestinal stromal tumor (GIST) after disease progression on orintolerance to imatinib mesylate. (1.1) Advanced renal cell carcinoma (RCC). (1.2) Progressive, well-differentiated pancreatic neuroendocrine tumors(pNET) in patients with unresectable locally advanced or metastaticdisease. (1.3)
DrugBank Targets:13 1. Platelet-derived growth factor receptor beta;2. Vascular endothelial growth factor receptor 1;3. Mast/stem cell growth factor receptor Kit;4. Vascular endothelial growth factor receptor 2;5. Vascular endothelial growth factor receptor 3;6. Receptor-type tyrosine-protein kinase FLT3;7. Macrophage colony-stimulating factor 1 receptor;8. Platelet-derived growth factor receptor alpha
Mechanism of Action:15 
Target: variety of kinases, platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factorreceptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3(FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factorreceptor (RET)
Action: inhibitor
FDA: Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), some of which areimplicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib wasevaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitorof platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factorreceptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3(FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factorreceptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical andcellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primarymetabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.Sunitinib inhibited the phosphorylation of multiple RTKs (PDGFR, VEGFR2, KIT) in tumor xenograftsexpressing RTK targets in vivo and demonstrated inhibition of tumor growth or tumor regression and/orinhibited metastases in some experimental models of cancer. Sunitinib demonstrated the ability to inhibitgrowth of tumor cells expressing dysregulated target RTKs (PDGFR, RET, or KIT) in vitro and to inhibitPDGFR- and VEGFR2-dependent tumor angiogenesis in vivo.
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Sylatron15 41 PEGINTERFERON ALFA-2B Merck April 2011
FDA Label: Sylatron
Disease/s that Drug Treats:melanoma
Indications and Usage:15 PegIntron is an antiviral indicated for treatment of Chronic Hepatitis C(CHC) in patients with compensated liver disease. (1.1)
DrugBank Targets:13 1. Interferon alpha/beta receptor 1;2. Interferon alpha/beta receptor 2
Mechanism of Action:15 
Target: innate antiviral immune response
Action: inducer
FDA: Pegylated recombinant human interferon alfa-2b is an inducer of the innate antiviral immune response [see Microbiology (12.4)].
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Synribo15 41 OMACETAXINE MEPESUCCINATE Teva Pharmaceutical October 2012
FDA Label: Synribo
Disease/s that Drug Treats:chronic or accelerated phase chronic myeloid leukemia
Indications and Usage:15 SYNRIBO for Injection is indicated for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI) (1)
DrugBank Targets:13 1. 50S ribosomal protein L2;2. 60S ribosomal protein L3
Mechanism of Action:15 
Target: A-site cleft in the peptidyl-transferase center of thelarge ribosomal subunit from a strain of archaeabacteria
Action: inhibitor of protein synthesis
FDA: The mechanism of action of omacetaxine mepesuccinate has not been fully elucidated but includes inhibition of protein synthesis andis independent of direct Bcr-Abl binding. Omacetaxine mepesuccinate binds to the A-site cleft in the peptidyl-transferase center of thelarge ribosomal subunit from a strain of archaeabacteria. In vitro, omacetaxine mepesuccinate reduced protein levels of the Bcr-Abloncoprotein and Mcl-1, an anti-apoptotic Bcl-2 family member. Omacetaxine mepesuccinate showed activity in mouse models ofwild-type and T315I mutated Bcr-Abl CML.
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Tafinlar15 41 DABRAFENIB MESYLATE GlaxoSmithKline May 2013
FDA Label: Tafinlar
Disease/s that Drug Treats:unresectable or metastatic melanoma with BRAF V600E mutation
Indications and Usage:15  TAFINLAR is a kinase inhibitor indicated as a single agent for thetreatment of patients with unresectable or metastatic melanoma withBRAF V600E mutation as detected by an FDA-approved test. (1.1, 2.1) TAFINLAR in combination with trametinib is indicated for the treatmentof patients with unresectable or metastatic melanoma with BRAF V600Eor V600K mutations as detected by an FDA-approved test. The use incombination is based on the demonstration of durable response rate.Improvement in disease-related symptoms or overall survival has notbeen demonstrated for TAFINLAR in combination with trametinib. (1.2,2.1, 14.2)Limitation of Use: TAFINLAR is not indicated for treatment of patients withwild-type BRAF melanoma. (1.3, 5.2)
DrugBank Targets:13 1. Serine/threonine-protein kinase B-raf;2. RAF proto-oncogene serine/threonine-protein kinase;3. Serine/threonine-protein kinase SIK1;4. Serine/threonine-protein kinase Nek11;5. LIM domain kinase 1
Mechanism of Action:15 
Target: some mutated forms of BRAF kinases, wild-type BRAF and CRAF kinases
Action: inhibitor
FDA: Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC50 values of0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes,respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2and 5.0 nM, respectively, and other kinases such as SIK1, NEK11, and LIMK1 at higherconcentrations. Some mutations in the BRAF gene, including those that result in BRAF V600E,can result in constitutively activated BRAF kinases that may stimulate tumor cell growth [seeIndications and Usage (1)]. Dabrafenib inhibits BRAF V600 mutation-positive melanoma cellgrowth in vitro and in vivo.Dabrafenib and trametinib target two different tyrosine kinases in the RAS/RAF/MEK/ERKpathway. Use of dabrafenib and trametinib in combination resulted in greater growth inhibitionof BRAF V600 mutation-positive melanoma cell lines in vitro and prolonged inhibition of tumorgrowth in BRAF V600 mutation positive melanoma xenografts compared with either drug alone.
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Tarceva15 41 ERLOTINIB HYDROCHLORIDE Genentech, OSI Pharmaceuticals November, 2004
FDA Label: Tarceva
Disease/s that Drug Treats:Non-small cell lung cancer
Indications and Usage:15 TARCEVA is a kinase inhibitor indicated for: First-line treatment of patients with metastatic non-small cell lungcancer (NSCLC) whose tumors have epidermal growth factor receptor(EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations asdetected by an FDA-approved test. (1.1) Maintenance treatment of patients with locally advanced or metastaticNSCLC whose disease has not progressed after four cycles of platinumbasedfirst-line chemotherapy. (1.1) Treatment of locally advanced or metastatic NSCLC after failure of atleast one prior chemotherapy regimen. (1.1) First-line treatment of patients with locally advanced, unresectable ormetastatic pancreatic cancer, in combination with gemcitabine. (1.2)
DrugBank Targets:13 1. Epidermal growth factor receptor;2. Nuclear receptor subfamily 1 group I member 2
Mechanism of Action:15 
Target: Human Epidermal Growth Factor Receptor Type 1/Epidermal Growth Factor Receptor (HER1/EGFR) tyrosine kinase
Action: inhibitor
FDA: Epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells. In some tumor cells signalingthrough this receptor plays a role in tumor cell survival and proliferation irrespective of EGFR mutation status. Erlotinib reversiblyinhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor and therebyinhibiting further downstream signaling. Erlotinib binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higherthan its affinity for the wild type receptor. Erlotinib inhibition of other tyrosine kinase receptors has not been fully characterized.
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Targretin 15 41 bexarotene VALEANT LUXEMBOURG 12/29/1999
FDA Label: Targretin
Disease/s that Drug Treats:cutaneous T-cell lymphoma
Indications and Usage:15 TARGRETIN (bexarotene) is a retinoid indicated for the treatment ofcutaneous manifestations of cutaneous T-cell lymphoma in patients who arerefractory to at least one prior systemic therapy. (1)
DrugBank Targets:13 1. Retinoic acid receptor RXR-alpha;2. Retinoic acid receptor RXR-beta;3. Retinoic acid receptor RXR-gamma
Mechanism of Action:15 
Target: retinoid X receptor subtypes (RXRalpha, RXRbeta, RXRgama)
Action: activator
FDA: Bexarotene selectively binds and activates retinoid X receptor subtypes (RXR, RXR, RXR).RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs),vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Onceactivated, these receptors function as transcription factors that regulate the expression of genes thatcontrol cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of sometumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivoin some animal models. The exact mechanism of action of bexarotene in the treatment of cutaneousT-cell lymphoma (CTCL) is unknown.
86
Tasigna15 41 NILOTINIB HYDROCHLORIDE MONOHYDRATE Novartis October 2007
FDA Label: Tasigna
Disease/s that Drug Treats:chronic myelogenous leukemia
Indications and Usage:15 Tasigna is a kinase inhibitor indicated for:The treatment of newly diagnosed adult patients with Philadelphiachromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase.The treatment of chronic phase (CP) and accelerated phase (AP) Ph+ CML inadult patients resistant to or intolerant to prior therapy that included imatinib.(1.2)--------------
DrugBank Targets:13 1. Tyrosine-protein kinase ABL1;2. Mast/stem cell growth factor receptor Kit
Mechanism of Action:15 
Target: Bcr-Abl kinase, c-kit and Platelet Derived Growth Factor (PDGF)
Action: inhibitor of signal transduction
FDA: Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation ofthe kinase domain of ABL protein. In vitro, nilotinib inhibited BCR-ABL mediated proliferation of murineleukemic cell lines and human cell lines derived from patients with Ph+ CML. Under the conditions of theassays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 outof 33 mutations tested. In vivo, nilotinib reduced the tumor size in a murine BCR-ABL xenograft model.Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: BCR-ABL (20to 60 nM), PDGFR (69 nM), c-KIT (210 nM), CSF-1R (125 to 250 nM), and DDR1 (3.7 nM).
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Taxotere15 41 DOCETAXEL Rhone Poulenc Rorer May 1996
FDA Label: Taxotere
Disease/s that Drug Treats:breast cancer
Indications and Usage:15 TAXOTERE is a microtubule inhibitor indicated for: Breast Cancer (BC): single agent for locally advanced or metastatic BCafter chemotherapy failure; and with doxorubicin andcyclophosphamide as adjuvant treatment of operable node-positive BC(1.1) Non-Small Cell Lung Cancer (NSCLC): single agent for locallyadvanced or metastatic NSCLC after platinum therapy failure; andwith cisplatin for unresectable, locally advanced or metastaticuntreated NSCLC (1.2) Hormone Refractory Prostate Cancer (HRPC): with prednisone inandrogen independent (hormone refractory) metastatic prostate cancer(1.3) Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil foruntreated, advanced GC, including the gastroesophageal junction (1.4) Squamous Cell Carcinoma of the Head and Neck Cancer (SCCHN):with cisplatin and fluorouracil for induction treatment of locallyadvanced SCCHN (1.5)
DrugBank Targets:13 1. Tubulin beta-1 chain;2. Apoptosis regulator Bcl-2;3. Microtubule-associated protein 2;4. Microtubule-associated protein 4;5. Microtubule-associated protein tau;6. Nuclear receptor subfamily 1 group I member 2
Mechanism of Action:15 
Target: free tubulin
Action: promoter of assembly
FDA: Docetaxel is an antineoplastic agent that acts by disrupting the microtubular network in cells that isessential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes theassembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. Thisleads to the production of microtubule bundles without normal function and to the stabilization ofmicrotubules, which results in the inhibition of mitosis in cells. Docetaxel’s binding to microtubulesdoes not alter the number of protofilaments in the bound microtubules, a feature which differs from mostspindle poisons currently in clinical use.
88
Treanda15 41 BENDAMUSTINE HYDROCHLORIDE Cephalon October 2008
FDA Label: Treanda
Disease/s that Drug Treats:Chronic lymphocytic leukemia and B-cell non-Hodgkin’s lymphoma
Indications and Usage:15 TREANDA is an alkylating drug indicated for treatment of patients with: Chronic lymphocytic leukemia (CLL). Efficacy relative to first linetherapies other than chlorambucil has not been established. (1.1) Indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed duringor within six months of treatment with rituximab or a rituximab-containingregimen. (1.2)
DrugBank Targets: -
Mechanism of Action:15 
Target: -
Action: -
FDA: Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like benzimidazole ring.Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electronrichnucleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to celldeath via several pathways. Bendamustine is active against both quiescent and dividing cells. The exact mechanism ofaction of bendamustine remains unknown.
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Trelstar Depot/ Trelstar LA15 TRIPTORELIN PAMOATE Debio Rechereche Pharmaceutique, Target Research Associates/ Debiopharm June 2000/ June 2001
Disease/s that Drug Treats:advanced prostate cancer/ Prostate cancer
Indications and Usage:15 TRELSTAR is a gonadotropin releasing hormone (GnRH) agonist indicated for the palliative treatmentof advanced prostate cancer. (1)
DrugBank Targets: -
Mechanism of Action:15 
Target: gonadotropin releasing hormone (GnRH)
Action: agonist
FDA: Triptorelin is a synthetic decapeptide agonist analog of gonadotropin releasing hormone (GnRH).Comparative in vitro studies showed that triptorelin was 100-fold more active than native GnRH instimulating luteinizing hormone release from monolayers of dispersed rat pituitary cells in culture and20-fold more active than native GnRH in displacing 125I-GnRH from pituitary receptor sites. In animalstudies, triptorelin pamoate was found to have 13‑fold higher luteinizing hormone-releasing activity and21-fold higher follicle-stimulating hormone-releasing activity compared to the native GnRH.
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Trisenox15 41 ARSENIC TRIOXIDE Cell Therapeutics September 2000
FDA Label: Trisenox
Disease/s that Drug Treats:Acute Promyelocytic Leukemia
Indications and Usage:15 TRISENOX is an arsenical indicated for induction of remission andconsolidation in patients with acute promyelocytic leukemia (APL) who arerefractory to, or have relapsed from, retinoid and anthracycline chemotherapy,and whose APL is characterized by the presence of the t(15;17) translocationor PML/RAR-alpha gene expression.
DrugBank Targets:13 1. Inhibitor of nuclear factor kappa-B kinase subunit beta;2. Thioredoxin reductase 1, cytoplasmic;3. Transcription factor AP-1;4. G1/S-specific cyclin-D1;5. Mitogen-activated protein kinase 3;6. Mitogen-activated protein kinase 1;7. RAC-alpha serine/threonine-protein kinase
Mechanism of Action:15 
Target: DNA/ promyelocytic leukemia (PML)-retinoic acid receptor (RAR)-alpha
Action: damager
FDA: The mechanism of action of TRISENOX is not completely understood. Arsenic trioxide causes morphologicalchanges and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells invitro. Arsenic trioxide also causes damage or degradation of the fusion protein promyelocytic leukemia (PML)-retinoic acid receptor (RAR)-alpha.
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Tykerb15 41 LAPATINIB DITOSYLATE GlaxoSmithKline March 2007
FDA Label: Tykerb
Disease/s that Drug Treats:breast cancer
Indications and Usage:15 TYKERB, a kinase inhibitor, is indicated in combination with: (1) capecitabine, for the treatment of patients with advanced or metastatic breastcancer whose tumors overexpress HER2 and who have received prior therapyincluding an anthracycline, a taxane, and trastuzumab.Limitation of Use: Patients should have disease progression on trastuzumabprior to initiation of treatment with TYKERB in combination with capecitabine. letrozole for the treatment of postmenopausal women with hormone receptorpositivemetastatic breast cancer that overexpresses the HER2 receptor forwhom hormonal therapy is indicated.TYKERB in combination with an aromatase inhibitor has not been comparedto a trastuzumab-containing chemotherapy regimen for the treatment ofmetastatic breast cancer.
DrugBank Targets:13 1. Epidermal growth factor receptor;2. Receptor tyrosine-protein kinase erbB-2
Mechanism of Action:15 
Target: Epidermal Growth Factor Receptor (EGFR [ErbB1]), Human Epidermal Receptor Type 2 (HER-2 [ErbB2]) receptor
Action: inhibitor intracellular tyrosine kinase domains
FDA: Lapatinib is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinasedomains of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and of Human EpidermalReceptor Type 2 (HER2 [ErbB2]) receptors (estimated Kiapp values of 3nM and 13nM,respectively) with a dissociation half-life of 300 minutes. Lapatinib inhibits ErbB-driven tumorcell growth in vitro and in various animal models.An additive effect was demonstrated in an in vitro study when lapatinib and 5-FU (theactive metabolite of capecitabine) were used in combination in the 4 tumor cell lines tested. Thegrowth inhibitory effects of lapatinib were evaluated in trastuzumab-conditioned cell lines.Lapatinib retained significant activity against breast cancer cell lines selected for long-termgrowth in trastuzumab-containing medi