MCID: BRR013
MIFTS: 57

Barrett Esophagus/esophageal Adenocarcinoma malady

Categories: Genetic diseases, Cancer diseases, Gastrointestinal diseases, Rare diseases

Aliases & Classifications for Barrett Esophagus/esophageal Adenocarcinoma

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Aliases & Descriptions for Barrett Esophagus/esophageal Adenocarcinoma:

Name: Barrett Esophagus/esophageal Adenocarcinoma 50 12
Barrett Esophagus 50 11 46 23 68 48 37 66
Barrett's Esophagus 11 46 13 25
Barrett's Ulcer of Esophagus 11 66
Adenocarcinoma of Esophagus 23 52
Chronic Peptic Ulcer and Esophagitis Syndrome 46
Barrett's Esophagus with Esophagitis 11
Malignant Neoplasm of Esophagus 66
Gastroesophageal Reflux Disease 66
Esophageal Adenocarcinoma 52
Esophagitis-Peptic Ulcer 46
Gastroesophageal Reflux 23
 
Columnar-Like Esophagus 46
Barrett's Oesophagus 11
Esophageal Carcinoma 66
Esophageal Neoplasms 66
Barrett Metaplasia 68
Esophageal Cancer 23
Barretts Syndrome 11
Barrett Syndrome 46
Barrett Ulcer 46
Cle 11
Be 68

Characteristics:

Orphanet epidemiological data:

52
adenocarcinoma of esophagus:
Inheritance: Not applicable; Prevalence: 1-9/100000 (Europe),1-9/1000000 (Worldwide); Age of onset: Adult; Age of death: adult

HPO:

62
barrett esophagus/esophageal adenocarcinoma:
Inheritance: somatic mutation


Classifications:



External Ids:

OMIM50 614266
Disease Ontology11 DOID:9206
ICD9CM30 530.85
MeSH37 D001471
NCIt43 C2891
Orphanet52 ORPHA99976
ICD10 via Orphanet29 C15.2, C15.5

Summaries for Barrett Esophagus/esophageal Adenocarcinoma

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NIH Rare Diseases:46 Barrett esophagus is a condition in which the lining of the esophagus (the tube that carries food from the throat to the stomach) is replaced by tissue that is similar to the lining of the intestines. although this change does not cause any specific signs or symptoms, it is typically diagnosed in people who have long-term gastroesophageal reflux disease (gerd). the exact underlying cause of barrett esophagus is not known; however, it generally occurs sporadically in people with no family history of the condition. treatment varies by the severity of the condition and generally includes medications and life style modifications to ease the symptoms of gerd. endoscopic or surgical treatments may be recommended in people with severe cases. last updated: 7/13/2015

MalaCards based summary: Barrett Esophagus/esophageal Adenocarcinoma, also known as barrett esophagus, is related to esophageal cancer and gastric cancer, and has symptoms including obesity, weight loss and feeding difficulties in infancy. An important gene associated with Barrett Esophagus/esophageal Adenocarcinoma is ASCC1 (Activating Signal Cointegrator 1 Complex Subunit 1), and among its related pathways are DNA damage_ATM/ATR regulation of G1/S checkpoint and Bladder cancer. The drugs cisplatin and methotrexate have been mentioned in the context of this disorder. Affiliated tissues include lung, breast and endothelial, and related mouse phenotypes are neoplasm and immune system.

UniProtKB/Swiss-Prot:68 Barrett esophagus: A condition characterized by a metaplastic change in which normal esophageal squamous epithelium is replaced by a columnar and intestinal-type epithelium. Patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The main cause of Barrett esophagus is gastroesophageal reflux. The retrograde movement of acid and bile salts from the stomach into the esophagus causes prolonged injury to the esophageal epithelium and induces chronic esophagitis, which in turn is believed to trigger the pathologic changes.

OMIM:50 Barrett esophagus, or Barrett metaplasia, describes the phenotypic change of normal esophageal squamous epithelium to a... (614266) more...

Related Diseases for Barrett Esophagus/esophageal Adenocarcinoma

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Diseases related to Barrett Esophagus/esophageal Adenocarcinoma via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50)    (show all 288)
idRelated DiseaseScoreTop Affiliating Genes
1esophageal cancer34.4CCND1, CDKN2A, CDX2, PTGS2, TP53
2gastric cancer31.0CCND1, CDKN2A, TP53
3colorectal cancer28.5CCND1, CDKN2A, CDX2, GAST, KRT20, MUC2
4tylosis with esophageal cancer12.3
5high-grade dysplasia in patients with barrett esophagus12.1
6esophageal cancer, childhood11.9
7prune belly syndrome11.7
8mungan syndrome11.3
9benign exophthalmos syndrome11.3
10esophagitis11.2
11salivary gland adenoid cystic carcinoma10.9CDKN2A, TP53
12biliary papillomatosis10.9CDKN2A, TP53
13leukoencephalopathy with vanishing white matter10.9
14emphysema, congenital lobar10.9
15skeletal tuberculosis10.9CCND1, CDKN2A
16infiltrating lipoma10.9PTGS2, TP53
17split hand split foot malformation autosomal recessive10.9CDKN2A, TP53
18oral leukoedema10.9KRT20, KRT7
19posterior cerebral artery infarction10.8ATP4A, PTGS2
20active cochleovestibular meniere's disease10.8CCND1, CDKN2A, PTGS2
21esophagus verrucous carcinoma10.8CDKN2A, PTGS2, TP53
22boylan dew greco syndrome10.8CCND1, CDKN2A, PTGS2
23signet ring basal cell carcinoma10.8KRT20, KRT7
24chronic eustachian salpingitis10.8CDX2, KRT20, TP53
25mediastinal melanocytic neurilemmoma10.8KRT20, KRT7
26congenital heart disease10.8CDX2, KRT20, PTGS2
27bladder verrucous squamous cell carcinoma10.8CCND1, CDKN2A, TP53
28stroma-dominant and stroma-poor composite ganglioneuroblastoma10.8CDKN2A, PTGS2, TP53
29apocrine adenocarcinoma10.8CDX2, MUC2, MUC6
30histoplasmosis meningitis10.8ATP4A, CDX2, PTGS2
31striated muscle rhabdoid tumor10.8CDX2, KRT20, TP53
32prostate signet ring cell adenocarcinoma10.8CDX2, KRT20, MUC2
33oligodendroglioma10.8CCND1, CDKN2A, TP53
34rectum adenoma10.8KRT20, KRT7
35adenoid squamous cell carcinoma10.8CDKN2A, TP53
36pigmented villonodular synovitis10.8CDX2, KRT7
37ductal carcinoma in situ10.8CCND1, CDKN2A, TP53
38histidine metabolism disease10.8CCND1, CDKN2A, TP53
39pancreatic endocrine carcinoma10.8MUC2, MUC6
40iris disease10.8CDX2, KRT20
41integumentary system cancer10.8CCND1, CDKN2A, TP53
42oral lichen planus10.8CCND1, PTGS2, TP53
43glottis squamous cell carcinoma10.8CDX2, MUC2, MUC5AC
44bilateral retinoblastoma10.8CCND1, CDKN2A, TP53
45desmoplastic infantile astrocytoma10.8CCND1, CDKN2A, PTGS2
46pharynx cancer10.8CCND1, CDKN2A, TP53
47moderately severe hemophilia a10.8MUC2, MUC5AC
48sphenoid sinus squamous cell carcinoma10.8KRT20, KRT7
49carbuncle10.8KRT20, MUC2
50learning disability10.8CDKN2A, PTGS2, TP53

Graphical network of the top 20 diseases related to Barrett Esophagus/esophageal Adenocarcinoma:



Diseases related to barrett esophagus/esophageal adenocarcinoma

Symptoms for Barrett Esophagus/esophageal Adenocarcinoma

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Clinical features from OMIM:

614266

Symptoms:

 52 (show all 10)
  • obesity
  • clinodactyly of the 5th toe
  • nausea and vomiting
  • gastroesophageal reflux
  • lymphadenopathy
  • feeding difficulties in infancy
  • esophageal carcinoma
  • cough
  • barrett esophagus
  • chest pain

HPO human phenotypes related to Barrett Esophagus/esophageal Adenocarcinoma:

(show all 11)
id Description Frequency HPO Source Accession
1 obesity hallmark (90%) HP:0001513
2 weight loss hallmark (90%) HP:0001824
3 feeding difficulties in infancy hallmark (90%) HP:0008872
4 barrett esophagus hallmark (90%) HP:0100580
5 abnormality of the abdominal organs hallmark (90%) HP:0002012
6 nausea and vomiting typical (50%) HP:0002017
7 chest pain typical (50%) HP:0100749
8 neoplasm typical (50%) HP:0002664
9 lymphadenopathy occasional (7.5%) HP:0002716
10 esophageal carcinoma HP:0011459
11 barrett esophagus HP:0100580

UMLS symptoms related to Barrett Esophagus/esophageal Adenocarcinoma:


abdominal pain, constipation, diarrhea, dyspepsia, heartburn, nausea and vomiting, swallowing problem, gastrointestinal gas, coughing, snoring, sore throat, vertigo/dizziness, equilibration disorder

Drugs & Therapeutics for Barrett Esophagus/esophageal Adenocarcinoma

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FDA approved drugs:

(show all 199)
id Drug Name Active Ingredient(s)16 Company Approval Date
1
Abstral16 FENTANYL (citrate) ProStrakan January 2011
FDA Label: Abstral
Disease/s that Drug Treats:breakthrough cancer pain in opiod-tolerant patients
Indications and Usage:16 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:14 1. Mu-type opioid receptor ;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:16 
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.
2
Actiq16 FENTANYL (citrate) Anesta Corporation November 1998
FDA Label: Actiq
Disease/s that Drug Treats:cancer pain
Indications and Usage:16 ACTIQ is an opioid agonist indicated for the management of breakthrough pain in cancer patients 16 years of age and older who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. (1) Limitations of Use: ACTIQ may be dispensed only to patients enrolled in the TIRF REMS Access program. (1)
DrugBank Targets:14 1. Mu-type opioid receptor ;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:16 
Target: -
Action: agonist
FDA: Fentanyl is a pure opioid agonist whose principal therapeutic action is analgesia. Other members of the class known as opioid agonists include substances such as morphine, oxycodone, hydromorphone, codeine, and hydrocodone.
3
Adcetris16 42 BRENTUXIMAB VEDOTIN Seattle Genetics August 2011
FDA Label: Adcetris
Disease/s that Drug Treats:Hodgkin lymphoma and anaplastic large cell lymphoma
Indications and Usage:16 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:14 Tumor necrosis factor receptor superfamily member 8
Mechanism of Action:16 
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 16 42 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:16 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:14 Serine/threonine-protein kinase mTOR
Mechanism of Action:16 
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
Akynzeo16 42 NETUPITANT AND PALONOSETRON (hydrochloride) Helsinn October 2014
FDA Label: Akynzeo
Disease/s that Drug Treats:chemotherapy-induced nausea and vomiting
Indications and Usage:16 AKYNZEO is a fixed combination of netupitant, a substance P/neurokinin 1(NK1) receptor antagonist, and palonosetron, a serotonin-3 (5-HT3) receptorantagonist indicated for the prevention of acute and delayed nausea andvomiting associated with initial and repeat courses of cancer chemotherapy,including, but not limited to, highly emetogenic chemotherapy. Oralpalonosetron prevents nausea and vomiting during the acute phase andnetupitant prevents nausea and vomiting during both the acute and delayedphase after cancer chemotherapy. (1)
DrugBank Targets:14 1. Substance-P receptor;2. 5-hydroxytryptamine receptor 3A
Mechanism of Action:16 
Target: neurokinin 1 (NK1) receptors/ substance P mediated responses [netupitant] & 5-HT3 receptor [palonosetron]
Action: activator/ inhibitor & agonist
FDA: Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK1) receptors.Palonosetron is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or noaffinity for other receptors. Cancer chemotherapy may be associated with a high incidence of nausea andvomiting, particularly when certain agents, such as cisplatin, are used. 5-HT3 receptors are located on thenerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the areapostrema. Chemotherapeutic agents produce nausea and vomiting by stimulating the release of serotoninfrom the enterochromaffin cells of the small intestine. Serotonin then activates 5-HT3 receptors located onvagal afferents to initiate the vomiting reflex. The development of acute emesis is known to depend onserotonin and its 5-HT3 receptors have been demonstrated to selectively stimulate the emetic response.Delayed emesis has been largely associated with the activation of tachykinin family neurokinin 1 (NK1)receptors (broadly distributed in the central and peripheral nervous systems) by substance P. As shown inin vitro and in vivo studies, netupitant inhibits substance P mediated responses.
6
Aloxi16 42 PALONOSETRON (hydrochloride) MGI Pharma, Helsinn Healthcare August 2003
FDA Label: Aloxi
Disease/s that Drug Treats:Chemotherapy side effects
Indications and Usage:16 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:14 5-hydroxytryptamine receptor 3A
Mechanism of Action:16 
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
Anexsia16 ACETAMINOPHEN; HYDROCODONE BITARTRATE Mallinckrodt Group August 1996
FDA Label: -
Disease/s that Drug Treats:chronic pain
Indications and Usage:16 -
DrugBank Targets:14 1. Prostaglandin G/H synthase 2;2. Prostaglandin G/H synthase 1;3. Prostaglandin G/H synthase 3;4. Mu-type opioid receptor;5. Delta-type opioid receptor
Mechanism of Action:16 
Target: cyclooxygenase (COX); OP1, OP2, and OP3 opiate receptors
Action: inhibitor; agonist
FDA: -
8
Aredia16 42 PAMIDRONATE DISODIUM Chiron August 1996
FDA Label: Aredia
Disease/s that Drug Treats:osteolytic bone metastases of breast cancer
Indications and Usage:16 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:14 1. Farnesyl pyrophosphate synthase;2. Hydroxylapatite
Mechanism of Action:16 
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.
9
Arimidex16 42 ANASTROZOLE AstraZeneca January 1996
FDA Label: Arimidex
Disease/s that Drug Treats:post menopausal breast cancer
Indications and Usage:16 ARIMIDEX is an aromatase inhibitor indicated for: Adjuvant treatment of postmenopausal women withhormone receptor-positive early breast cancer (1.1) First-line treatment of postmenopausal women withhormone receptor-positive or hormone receptor unknownlocally advanced or metastatic breast cancer (1.2) Treatment of advanced breast cancer in postmenopausalwomen with disease progression following tamoxifentherapy. Patients with ER-negative disease and patientswho did not respond to previous tamoxifen therapy rarelyresponded to ARIMIDEX (1.3)
DrugBank Targets:14 Cytochrome P450 19A1
Mechanism of Action:16 
Target: oral aromatase
Action: inhibitor
FDA: The growth of many cancers of the breast is stimulated or maintained by estrogens.In postmenopausal women, estrogens are mainly derived from the action of the aromataseenzyme, which converts adrenal androgens (primarily androstenedione and testosterone) toestrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and inthe cancer tissue itself can therefore be achieved by specifically inhibiting the aromataseenzyme.Anastrozole is a selective non-steroidal aromatase inhibitor. It significantly lowers serumestradiol concentrations and has no detectable effect on formation of adrenal corticosteroidsor aldosterone.
10
Aromasin Tablets16 42 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:16 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:14 Cytochrome P450 19A1
Mechanism of Action:16 
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.
11
Arranon16 42 NELARABINE GlaxoSmithKline October 2005
FDA Label: Arranon
Disease/s that Drug Treats:Lymphoblastic Leukemia
Indications and Usage:16 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:14 DNA
Mechanism of Action:16 
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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12
Beleodaq16 42 BELINOSTAT Spectrum Pharmaceuticals July 2014
FDA Label: Beleodaq
Disease/s that Drug Treats:relapsed or refractory peripheral T-cell lymphoma
Indications and Usage:16 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:14 no entry
Mechanism of Action:16 
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
Blincyto16 42 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:16 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:14 1. B-lymphocyte antigen CD19;2. T-cell surface glycoprotein CD3 delta chain
Mechanism of Action:16 
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.
14
Busulfex16 42 BUSULFAN Orphan Medical February 1999
FDA Label: Busulfex
Disease/s that Drug Treats:leukemia
Indications and Usage:16 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:14 DNA
Mechanism of Action:16 
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.
15
Campostar16 42 IRINOTECAN HYDROCHLORIDE Pharmacia & Upjohn June 1996
FDA Label: Campostar
Disease/s that Drug Treats:metastatic colorectal cancer
Indications and Usage:16 CAMPTOSAR is a topoisomerase inhibitor indicated for: First-line therapy in combination with 5-fluorouracil and leucovorin forpatients with metastatic carcinoma of the colon or rectum. (1) Patients with metastatic carcinoma of the colon or rectum whose diseasehas recurred or progressed following initial fluorouracil-based therapy. (1)
DrugBank Targets:14 1. DNA topoisomerase I, mitochondrial;2. DNA topoisomerase 1
Mechanism of Action:16 
Target: topoisomerase I-DNA complex
Action: inhibitor of repairs to DNA
FDA: Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzymetopoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strandbreaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complexand prevent religation of these single-strand breaks. Current research suggests that thecytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesiswhen replication enzymes interact with the ternary complex formed by topoisomerase I, DNA,and either irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strandbreaks.
16
Cervarix16 42 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:16 -
DrugBank Targets: -
Mechanism of Action:16 
Target: IgG neutralizing antibodies directed against HPV-L1 capsid proteins
Action: activates/ provokes production
FDA: -
17
Clolar16 42 CLOFARABINE Genzyme December, 2004
FDA Label: Clolar
Disease/s that Drug Treats:Lymphoblastic Leukemia
Indications and Usage:16 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:14 1. DNA polymerase alpha catalytic subunit;2. Ribonucleoside-diphosphate reductase large subunit;3. DNA
Mechanism of Action:16 
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.
18
Cometriq16 42 CABOZANTINIB S-MALATE Exelixis November 2012
FDA Label: Cometriq
Disease/s that Drug Treats:thyroid cancer
Indications and Usage:16 COMETRIQ is a kinase inhibitor indicated for the treatment ofpatients with progressive, metastatic medullary thyroid cancer(MTC). (1)
DrugBank Targets:14 1. Hepatocyte growth factor receptor;2. Vascular endothelial growth factor receptor 2;3. Proto-oncogene tyrosine-protein kinase receptor Ret
Mechanism of Action:16 
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.
19
Degarelix16 42 degarelix Ferring Pharmaceuticals December of 2008
FDA Label: -
Disease/s that Drug Treats:Prostate Cancer
Indications and Usage:16 -
DrugBank Targets:14 1. Gonadotropin-releasing hormone receptor
Mechanism of Action:16 
Target: Gonadotropin-releasing hormone (GnRH) receptor
Action: antagonist
FDA: -
20
Elitek16 42 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:16 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:14 1. Uric acid
Mechanism of Action:16 
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).
21
Ellence16 42 EPIRUBICIN HYDROCHLORIDE Pharmacia & Upjohn September 1999
FDA Label: Ellence
Disease/s that Drug Treats:Component of adjuvant therapy in patients with evidence of axillary node tumor involvement for primary breast cancer
Indications and Usage:16 ELLENCE Injection is an anthracycline topoisomerase II inhibitor indicatedas a component of adjuvant therapy in patients with evidence of axillary nodetumor involvement following resection of primary breast cancer (1).
DrugBank Targets:14 1. Chromodomain-helicase-DNA-binding protein 1;2. DNA topoisomerase 2-alpha;3. DNA
Mechanism of Action:16 
Target: nucleic acid (DNA and RNA) and protein synthesis
Action: inhibitor
FDA: Epirubicin is an anthracycline cytotoxic agent. Although it is known that anthracyclines can interfere with a number of biochemical andbiological functions within eukaryotic cells, the precise mechanisms of epirubicin’s cytotoxic and/or antiproliferative properties have not beencompletely elucidated.Epirubicin forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs, with consequent inhibition of nucleicacid (DNA and RNA) and protein synthesis.Such intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Epirubicin also inhibits DNA helicase activity,preventing the enzymatic separation of double-stranded DNA and interfering with replication and transcription. Epirubicin is also involved inoxidation/reduction reactions by generating cytotoxic free radicals. The antiproliferative and cytotoxic activity of epirubicin is thought to resultfrom these or other possible mechanisms.Epirubicin is cytotoxic in vitro to a variety of established murine and human cell lines and primary cultures of human tumors. It is also activein vivo against a variety of murine tumors and human xenografts in athymic mice, including breast tumors.
22
Eloxatin16 42 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:16 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:14 1. DNA
Mechanism of Action:16 
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)].
23
Erwinaze16 42 asparaginase Erwinia chrysanthemi Eusa Pharma November of 2011
FDA Label: Erwinaze
Disease/s that Drug Treats:acute lymphoblastic leukemia
Indications and Usage:16 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:14 -
Mechanism of Action:16 
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.
24
Ethyol16 AMIFOSTINE Alza December 8, 1995
FDA Label: Ethyol
Disease/s that Drug Treats:ovarian cancer
Indications and Usage:16 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:14 1. Ectonucleotide pyrophosphatase/phosphodiesterase family member 1;2. Alkaline phosphatase, placental-like
Mechanism of Action:16 
Target: -
Action: -
FDA: -
25
Eulexin16 FLUTAMIDE Schering-Plough June 1996
FDA Label: Eulexin
Disease/s that Drug Treats:prostate cancer
Indications and Usage:16 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:14 1. Androgen receptor;2. Aryl hydrocarbon receptor
Mechanism of Action:16 
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.
26
Evista16 42 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:16 EVISTA is an estrogen agonist/antagonist indicated for Treatment and prevention of osteoporosis in postmenopausal women.(1.1)
DrugBank Targets:14 1. Estrogen receptor;2. Estrogen receptor beta
Mechanism of Action:16 
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.
27
Farydak16 42 PANOBINOSTAT LACTATE Novartis February 2015
FDA Label: Farydak
Disease/s that Drug Treats:Multiple myeloma
Indications and Usage:16 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:16 
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.
28
Faslodex16 42 FULVESTRANT AstraZeneca April 2002
FDA Label: Faslodex
Disease/s that Drug Treats:Hormone receptor positive metastatic breast cancer
Indications and Usage:16 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:14 1. Estrogen receptor
Mechanism of Action:16 
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.
29
Folotyn16 42 PRALATREXATE Allos Therapeutics September 2009
FDA Label: Folotyn
Disease/s that Drug Treats:peripheral T-cell lymphoma
Indications and Usage:16 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:14 1. Dihydrofolate reductase;2. Thymidylate synthase
Mechanism of Action:16 
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.
30
Fusilev16 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:16 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:14 1. Thymidylate synthase
Mechanism of Action:16 
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.
31
Gardasil16 42 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:16 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:16 
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.
32
Gemzar16 42 GEMCITABINE HYDROCHLORIDE Eli Lilly May 1996
FDA Label: Gemzar
Disease/s that Drug Treats:pancreatic cancer/Lung cancer
Indications and Usage:16 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:14 1. DNA;2. Ribonucleoside-diphosphate reductase large subunit;3. Thymidylate synthase;4. UMP-CMP kinase
Mechanism of Action:16 
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.
33
Gilotrif16 42 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:16 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:14 1. Epidermal growth factor receptor;2. Receptor tyrosine-protein kinase erbB-2;3. Receptor tyrosine-protein kinase erbB-4
Mechanism of Action:16 
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.
34
Hycamtin16 42 TOPOTECAN HYDROCHLORIDE GlaxoSmithKline/ SmithKline Beecham October 2007/ May 1996
FDA Label: Hycamtin
Disease/s that Drug Treats:small cell lung cancer/ ovarian cancer
Indications and Usage:16 HYCAMTIN for injection is a topoisomerase inhibitor indicated for: metastatic carcinoma of the ovary after disease progression on or afterinitial or subsequent chemotherapy. (1.1) small cell lung cancer platinum-sensitive disease in patients whoprogressed after first-line chemotherapy. (1.2) combination therapy with cisplatin for Stage IV-B, recurrent, orpersistent carcinoma of the cervix which is not amenable to curativetreatment. (1.3)
DrugBank Targets:14 1. DNA topoisomerase 1;2. DNA topoisomerase I, mitochondrial;3. DNA
Mechanism of Action:16 
Target: topoisomerase I
Action: inhibitor
FDA: Topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks.Topotecan binds to the topoisomerase I-DNA complex and prevents re-ligation of these singlestrandbreaks. The cytotoxicity of topotecan is thought to be due to double-strand DNA damageproduced during DNA synthesis, when replication enzymes interact with the ternary complexformed by topotecan, topoisomerase I, and DNA. Mammalian cells cannot efficiently repairthese double-strand breaks.
35
Ibrance16 42 PALBOCICLIB Pfizer February 2015
FDA Label: Ibrance
Disease/s that Drug Treats:ER-positive, HER2-negative breast cancer
Indications and Usage:16 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:14 1. Cyclin-dependent kinase 4;2. Cyclin-dependent kinase 6
Mechanism of Action:16 
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.
36
Iclusig16 42 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:16 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:14 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:16 
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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Imbruvica16 42 IBRUTINIB Pharmacyclics November of 2013/ February 2014
FDA Label: Imbruvica
Disease/s that Drug Treats:mantle cell lymphoma/chronic lymphocytic leukemia
Indications and Usage:16 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:14 1. Tyrosine-protein kinase BTK
Mechanism of Action:16 
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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Inlyta16 42 AXITINIB Pfizer January 2012
FDA Label: Inlyta
Disease/s that Drug Treats:advanced renal cell carcinoma
Indications and Usage:16 INLYTA is a kinase inhibitor indicated for the treatment of advancedrenal cell carcinoma after failure of one prior systemic therapy. (1)
DrugBank Targets:14 1. Vascular endothelial growth factor receptor 1;2. Vascular endothelial growth factor receptor 2;3. Vascular endothelial growth factor receptor 3
Mechanism of Action:16 
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 A16 42 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:16 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:14 1. Interferon alpha/beta receptor 2;2. Interferon alpha/beta receptor 1
Mechanism of Action:16 
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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Iressa16 42 GEFITINIB AstraZeneca May 2003
FDA Label: Iressa
Disease/s that Drug Treats:Non-Small-Cell Lung Cancer
Indications and Usage:16 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:14 1. Epidermal growth factor receptor
Mechanism of Action:16 
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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Istodax16 42 ROMIDEPSIN Gloucester Pharmaceuticals November 2009
FDA Label: Istodax
Disease/s that Drug Treats:cutaneous T-cell lymphoma
Indications and Usage:16 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:14 -
Mechanism of Action:16 
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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Ixempra16 42 IXABEPILONE Bristol-Myers Squibb October 2007
FDA Label: Ixempra
Disease/s that Drug Treats:Breast cancer
Indications and Usage:16 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:14 1. Tubulin beta-3 chain
Mechanism of Action:16 
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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Jevtana16 42 CABAZITAXEL sanofi aventis June 2010
FDA Label: Jevtana
Disease/s that Drug Treats:prostate cancer
Indications and Usage:16 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:14 1. Tubulin alpha-4A chain;2. Tubulin beta-1 chain
Mechanism of Action:16 
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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Kadcyla16 42 ADO-TRASTUZUMAB EMTANSINE Genentech February 2013
FDA Label: Kadcyla
Disease/s that Drug Treats:HER2-positive metastatic breast cancer
Indications and Usage:16 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:14 1. Receptor tyrosine-protein kinase erbB-2
Mechanism of Action:16 
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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Kadian16 MORPHINE SULFATE Purepac Pharmaceutical July 1996
FDA Label: Kadian
Disease/s that Drug Treats:chronic pain
Indications and Usage:16 KADIAN is an opioid agonist indicated for the management of pain severeenough to require daily, around-the-clock, long-term opioid treatment and forwhich alternative treatment options are inadequate.Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even atrecommended doses, and because of the greater risks of overdose anddeath with extended-release opioid formulations, reserve KADIAN foruse in patients for whom alternative treatment options (e.g., non-opioidanalgesics or immediate-release opioids) are ineffective, not tolerated, orwould be otherwise inadequate to provide sufficient management of pain. KADIAN is not indicated as an as-needed (prn) analgesic.
DrugBank Targets:14 1. Mu-type opioid receptor;2. Kappa-type opioid receptor;3. Delta-type opioid receptor
Mechanism of Action:16 
Target: opioid receptors
Action: agonist
FDA: Morphine sulfate, an opioid agonist, is relatively selective for the mu receptor, although it can interactwith other opioid receptors at higher doses. In addition to analgesia, the widely diverse effects ofmorphine sulfate include analgesia, dysphoria, euphoria, somnolence, respiratory depression, diminishedgastrointestinal motility, altered circulatory dynamics, histamine release, physical dependence, andalterations of the endocrine and autonomic nervous systems.Morphine produces both its therapeutic and its adverse effects by interaction with one or more classes ofspecific opioid receptors located throughout the body. Morphine acts as a full agonist, binding with andactivating opioid receptors at sites in the peri-aqueductal and peri-ventricular grey matter, the ventromedialmedulla and the spinal cord to produce analgesia.
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Keytruda16 42 PEMBROLIZUMAB Merck September 2014
FDA Label: Keytruda
Disease/s that Drug Treats:unresectable or metastatic melanoma
Indications and Usage:16 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:14 1. Programmed cell death protein 1
Mechanism of Action:16 
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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Kyprolis16 42 CARFILZOMIB Onyx Pharmaceuticals July 2012
FDA Label: Kyprolis
Disease/s that Drug Treats:multiple myeloma
Indications and Usage:16 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:14 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:16 
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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Lazanda16 FENTANYL CITRATE Archimedes June 2011
FDA Label: Lazanda
Disease/s that Drug Treats:breakthrough cancer pain
Indications and Usage:16 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:14 1. Mu-type opioid receptor;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:16 
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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Lenvima16 42 LENVATINIB MESYLATE Eisai February 2015
FDA Label: Lenvima
Disease/s that Drug Treats:thyroid cancer
Indications and Usage:16 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:14 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:16 
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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Leukine16 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:16 -
DrugBank Targets:14 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:16 
Target: -
Action: -
FDA: -
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Lupron Depot16 42 LEUPROLIDE ACETATE TAP Pharmaceuticals/ Abbott Laboratories July 1997/ January 1996
FDA Label: Lupron Depot
Disease/s that Drug Treats:prostate cancer
Indications and Usage:16 LUPRON DEPOT is a gonadotropin releasing hormone (GnRH) agonistindicated for: palliative treatment of advanced prostatic cancer. (1)
DrugBank Targets:14 1. Gonadotropin-releasing hormone receptor
Mechanism of Action:16 
Target: GnRH
Action: agonist
FDA: Leuprolide acetate, a GnRH agonist, acts as an inhibitor of gonadotropin secretion. Animalstudies indicate that following an initial stimulation, continuous administration of leuprolideacetate results in suppression of ovarian and testicular steroidogenesis. This effect was reversibleupon discontinuation of drug therapy.Administration of leuprolide acetate has resulted in inhibition of the growth of certain hormonedependent tumors (prostatic tumors in Noble and Dunning male rats and DMBA-inducedmammary tumors in female rats) as well as atrophy of the reproductive organs.
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Lynparza16 42 OLAPARIB AstraZeneca December 2014
FDA Label: Lynparza
Disease/s that Drug Treats:previously treated BRCA mutated advanced ovarian cancer
Indications and Usage:16 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:14 1. Poly [ADP-ribose] polymerase 1;2. Poly [ADP-ribose] polymerase 2;3. Poly [ADP-ribose] polymerase 3
Mechanism of Action:16 
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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Miraluma Test16 TECHNETIUM TC-99M SESTAMIBI KIT DuPont Merck Pharmaceutical Company May 1997
FDA Label: Miraluma Test
Disease/s that Drug Treats:breast imaging
Indications and Usage:16 Breast Imaging: MIRALUMA, Kit for the Preparation of Technetium Tc99m Sestamibi for Injection, is indicated for planar imaging as a second line diagnostic drug after mammography to assist in the evaluation of breast lesions in patients with an abnormal mammogram or a palpable breast mass. MIRALUMA is not indicated for breast cancer screening, to confirm the presence or absence of malignancy, and it is not an alternative to biopsy.
DrugBank Targets: -
Mechanism of Action:16 
Target: malignant cells
Action: accumulates
FDA: The mechanism of Tc99m Sestanibi localization in various types of breast tissue (e.g. beinign, inflammatory, malignant, fiborous) has not been established.
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Mozobil16 42 PLERIXAFOR Genzyme December 2008
FDA Label: Mozobil
Disease/s that Drug Treats:non-Hodgkin’s lymphoma and multiple myeloma
Indications and Usage:16 Mozobil, a hematopoietic stem cell mobilizer, is indicated in combinationwith granulocyte-colony stimulating factor (G-CSF) to mobilizehematopoietic stem cells (HSCs) to the peripheral blood for collection andsubsequent autologous transplantation in patients with non-Hodgkin’slymphoma and multiple myeloma. (1)
DrugBank Targets:14 1. C-X-C chemokine receptor type 4
Mechanism of Action:16 
Target: hematopoietic stem cell/ CXCR4 chemokine receptor
Action: monilizer/ inhibitor
FDA: Plerixafor is an inhibitor of the CXCR4 chemokine receptor and blocks binding of its cognateligand, stromal cell-derived factor-1α (SDF-1α). SDF-1α and CXCR4 are recognized to play arole in the trafficking and homing of human hematopoietic stem cells (HSCs) to the marrowcompartment. Once in the marrow, stem cell CXCR4 can act to help anchor these cells to themarrow matrix, either directly via SDF-1α or through the induction of other adhesion molecules.Treatment with plerixafor resulted in leukocytosis and elevations in circulating hematopoieticprogenitor cells in mice, dogs and humans. CD34+ cells mobilized by plerixafor were capable ofengraftment with long-term repopulating capacity up to one year in canine transplantationmodels.
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Nexavar16 42 SORAFENIB TOSYLATE Bayer/Onyx December 2005
FDA Label: Nexavar
Disease/s that Drug Treats:Renal Cell Carcinoma
Indications and Usage:16 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:14 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:16 
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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Nolvadex16 42 TAMOXIFEN CITRATE AstraZeneca October 1998
FDA Label: Nolvadex
Disease/s that Drug Treats:Breast Cancer
Indications and Usage:16 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:14 1. Estrogen receptor;2. Estrogen receptor beta;3. 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase;4. Protein kinase C
Mechanism of Action:16 
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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Onsolis16 FENTANYL CITRATE BioDelivery Sciences July 2009
FDA Label: Onsolis
Disease/s that Drug Treats:breakthrough cancer pain
Indications and Usage:16 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:14 1. Mu-type opioid receptor;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:16 
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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Opdivo16 42 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:16 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:14 1. Programmed cell death protein 1
Mechanism of Action:16 
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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Perjeta16 42 PERTUZUMAB Genentech June 2012
FDA Label: Perjeta
Disease/s that Drug Treats:HER2+ metastatic breast cancer
Indications and Usage:16 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:14 1. Receptor tyrosine-protein kinase erbB-2
Mechanism of Action:16 
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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Photodynamic Therapy (& Photofrin)16 PORFIMER SODIUM Sanofi-aventis January, 1996
Disease/s that Drug Treats:esophageal cancer
Indications and Usage:16 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: -
Mechanism of Action:16 
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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Photofrin16 PORFIMER SODIUM QLT January 1998
FDA Label: Photofrin
Disease/s that Drug Treats:Non-small cell lung cancer
Indications and Usage:16 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:14 1. Low-density lipoprotein receptor;2. High affinity immunoglobulin gamma Fc receptor I
Mechanism of Action:16 
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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Plenaxis16 ABARELIX Praecis Pharmaceuticals December 2003
FDA Label: Plenaxis
Disease/s that Drug Treats:Prostate Cancer
Indications and Usage:16 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:14 1. Gonadotropin-releasing hormone receptor
Mechanism of Action:16 
Target: GnRH receptors in the pituitary gland
Action: competitive blocker
FDA: -
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Pomalyst16 42 POMALIDOMIDE Celgene February 2013
FDA Label: Pomalyst
Disease/s that Drug Treats:relapsed and refractory multiple myeloma
Indications and Usage:16 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:14 1. Protein cereblon;2. Tumor necrosis factor;3. Prostaglandin G/H synthase 2
Mechanism of Action:16 
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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Premarin16 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:16 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:14 1. Estrogen receptor
Mechanism of Action:16 
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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Quadramet16 SAMARIUM SM-153 LEXIDRONAM PENTASODIUM DuPont Merck Pharmaceutical Company March 1997
FDA Label: -
Disease/s that Drug Treats:pain associated with bone cancer
Indications and Usage:16 -
DrugBank Targets: -
Mechanism of Action:16 
Target: osteoblastic tumor sites
Action: irradiator
FDA: -
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Revlimid16 42 LENALIDOMIDE Celgene June 2013
FDA Label: Revlimid
Disease/s that Drug Treats:mantle cell lymphoma
Indications and Usage:16 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:14 1. Protein cereblon;2. Tumor necrosis factor ligand superfamily member 11;3. Cadherin-5;4. Prostaglandin G/H synthase 2
Mechanism of Action:16 
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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Rituxan16 42 RITUXIMAB Biogen IDEC, Genentech November 1997
FDA Label: Rituxan
Disease/s that Drug Treats:non-hodgkin's lymphoma
Indications and Usage:16 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:14 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:16 
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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Sancuso16 GRANISETRON ProStrakan September 2008
FDA Label: Sancuso
Disease/s that Drug Treats:chemotherapy-induced nausea and vomiting
Indications and Usage:16 Sancuso is a serotonin subtype 3 (5-HT3) receptor antagonist indicated for theprevention of nausea and vomiting in patients receiving moderately and/orhighly emetogenic chemotherapy for up to 5 consecutive days. (1)
DrugBank Targets:14 1. 5-hydroxytryptamine receptor 3A
Mechanism of Action:16 
Target: 5-hydroxytryptamine3 (5-HT3) receptor
Action: agonist
FDA: Granisetron is a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist with little or no affinityfor other serotonin receptors, including 5-HT1, 5-HT1A, 5-HT1B/C, 5-HT2; for alpha1-, alpha2-, or betaadrenoreceptors;for dopamine-D2; or for histamine-H1; benzodiazepine; picrotoxin or opioidreceptors.Serotonin receptors of the 5-HT3 type are located peripherally on vagal nerve terminals and centrallyin the chemoreceptor trigger zone of the area postrema. During chemotherapy that inducesvomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HT3 receptors. Thisevokes vagal afferent discharge, inducing vomiting. Animal studies demonstrate that, in binding to5-HT3 receptors, granisetron blocks serotonin stimulation and subsequent vomiting after emetogenicstimuli such as cisplatin. In the ferret animal model, a single granisetron injection preventedvomiting due to high-dose cisplatin or arrested vomiting within 5 to 30 seconds.
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Sclerosol Intrapleural Aerosol16 42 TALC Bryan Corporation January 1998
Disease/s that Drug Treats:malignant pleural effusions
Indications and Usage:16 Sclerosol® Intrapleural Aerosol, administered by aerosol during thoracoscopy or openthoracotomy, is indicated to prevent recurrence of malignant pleural effusions in symptomaticpatients.
DrugBank Targets: -
Mechanism of Action:16 
Target: pleural cavity
Action: inducer of inflammatory reaction
FDA: The therapeutic action of talc instilled into the pleural cavity is thought to result from inductionof an inflammatory reaction. This reaction promotes adherence of the visceral to the parietalpleura, obliterating the pleural space and preventing reaccumulation of pleural fluid. The extentof talc systemically absorbed after intrapleural administration has not been adequately studied.Systemic exposure could be affected by the integrity of the visceral pleura, and therefore couldbe increased if talc is administered immediately following lung resection or biopsy.
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Self-examination breast pad16 Inventive Products on December 22, 1995
FDA Label: -
Disease/s that Drug Treats:breast self-examination
Indications and Usage:16 -
DrugBank Targets: -
Mechanism of Action:16 
Target: -
Action: -
FDA: -
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Sensipar16 CINACALCET HYDROCHLORIDE Amgen March 2004
FDA Label: Sensipar
Disease/s that Drug Treats:Hyperparathyroidism / Hypercalcemia
Indications and Usage:16 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:14 1. Extracellular calcium-sensing receptor
Mechanism of Action:16 
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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Sprycel16 42 DASATINIB Bristol-Myers Squibb June 2006
FDA Label: Sprycel
Disease/s that Drug Treats:Chronic Myeloid Leukemia
Indications and Usage:16 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:14 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:16 
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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Stivarga16 42 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:16 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:14 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:16 
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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Subsys16 FENTANYL Insys Therapeutics January of 2012
FDA Label: Subsys
Disease/s that Drug Treats:breakthrough cancer pain
Indications and Usage:16 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:14 1. Mu-type opioid receptor;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:16 
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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Sutent16 42 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:16 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:14 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:16 
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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Synercid I.V.16 DALFOPRISTIN; QUINUPRISTIN QUINUPRISTIN; DALFOPRISTIN Rhone Poulenc Rorer September 1999
FDA Label: Synercid I.V.
Disease/s that Drug Treats:For serious or life-threatening infections associated w/ vancomycin-resistant Enterococcus faecium (VREF) bacteremia.
Indications and Usage:16 Synercid is indicated in adults for the treatment of the following infections when caused bysusceptible strains of the designated microorganisms.Complicated skin and skin structure infections caused by Staphylococcus aureus (methicillinsusceptible) or Streptococcus pyogenes. (See CLINICAL STUDIES.)
DrugBank Targets:14 14 1. Streptogramin A acetyltransferase| 1. 23S rRNA;2. 50S ribosomal protein L10;3. 50S ribosomal protein L22
Mechanism of Action:16 
Target: bacterial ribosome - protien synthesis
Action: inhibitor
FDA: The site of action of quinupristin and dalfopristin is the bacterial ribosome. Dalfopristin has beenshown to inhibit the early phase of protein synthesis while quinupristin inhibits the late phase ofprotein synthesis. Synercid is bactericidal against isolates of methicillin-susceptible andmethicillin-resistant staphylococci. The mode of action of Synercid differs from that of otherclasses of antibacterial agents such as ß-lactams, aminoglycosides, glycopeptides, quinolones,macrolides, lincosamides and tetracyclines. Therefore, there is no cross resistance betweenSynercid and these agents when tested by the minimum inhibitory concentration (MIC) method.
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Synribo16 42 OMACETAXINE MEPESUCCINATE Teva Pharmaceutical October 2012
FDA Label: Synribo
Disease/s that Drug Treats:chronic or accelerated phase chronic myeloid leukemia
Indications and Usage:16 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:14 1. 50S ribosomal protein L2;2. 60S ribosomal protein L3
Mechanism of Action:16 
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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Tafinlar16 42 DABRAFENIB MESYLATE GlaxoSmithKline May 2013
FDA Label: Tafinlar
Disease/s that Drug Treats:unresectable or metastatic melanoma with BRAF V600E mutation
Indications and Usage:16  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:14 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:16 
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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Tarceva16 42 ERLOTINIB HYDROCHLORIDE Genentech, OSI Pharmaceuticals November, 2004
FDA Label: Tarceva
Disease/s that Drug Treats:Non-small cell lung cancer
Indications and Usage:16 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:14 1. Epidermal growth factor receptor;2. Nuclear receptor subfamily 1 group I member 2
Mechanism of Action:16 
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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Tasigna16 42 NILOTINIB HYDROCHLORIDE MONOHYDRATE Novartis October 2007
FDA Label: Tasigna
Disease/s that Drug Treats:chronic myelogenous leukemia
Indications and Usage:16 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:14 1. Tyrosine-protein kinase ABL1;2. Mast/stem cell growth factor receptor Kit
Mechanism of Action:16 
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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Taxotere16 42 DOCETAXEL Rhone Poulenc Rorer May 1996
FDA Label: Taxotere
Disease/s that Drug Treats:breast cancer
Indications and Usage:16 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:14 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:16 
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.
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Torisel16 42 TEMSIROLIMUS Wyeth May 2007
FDA Label: Torisel
Disease/s that Drug Treats:renal cell carcinoma
Indications and Usage:16 TORISEL® is a kinase inhibitor indicated for the treatment of advanced renalcell carcinoma. (1)
DrugBank Targets:14 1. Serine/threonine-protein kinase mTOR
Mechanism of Action:16 
Target: mTOR
Action: inhibitor
FDA: Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds toan intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTORthat controls cell division. Inhibition of mTOR activity resulted in a G1 growth arrest in treatedtumor cells. When mTOR was inhibited, its ability to phosphorylate p70S6k and S6 ribosomalprotein, which are downstream of mTOR in the PI3 kinase/AKT pathway was blocked. Inin vitro studies using renal cell carcinoma cell lines, temsirolimus inhibited the activity of mTORand resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha, and thevascular endothelial growth factor.
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Treanda16 42 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:16 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:16 
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 LA16 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:16 TRELSTAR is a gonadotropin releasing hormone (GnRH) agonist indicated for the palliative treatmentof advanced prostate cancer. (1)
DrugBank Targets: -
Mechanism of Action:16 
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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Trisenox16 42 ARSENIC TRIOXIDE Cell Therapeutics September 2000
FDA Label: Trisenox
Disease/s that Drug Treats:Acute Promyelocytic Leukemia
Indications and Usage:16 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:14 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:16 
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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Tykerb16 42 LAPATINIB DITOSYLATE GlaxoSmithKline March 2007
FDA Label: Tykerb
Disease/s that Drug Treats:breast cancer
Indications and Usage:16 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:14 1. Epidermal growth factor receptor;2. Receptor tyrosine-protein kinase erbB-2
Mechanism of Action:16 
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 medium in vitro. These in vitro findings suggest non-crossresistancebetween these two agents.Hormone receptor-positive breast cancer cells (with ER [Estrogen Receptor] and/or PgR[Progesterone Receptor]) that coexpress the HER2 tend to be resistant to established endocrinetherapies. Similarly, hormone receptor-positive breast cancer cells that initially lack EGFR orHER2 upregulate these receptor proteins as the tumor becomes resistant to endocrine therapy.
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Unituxin16 42 DINUTUXIMAB United Therapeutics March 2015
FDA Label: Unituxin
Disease/s that Drug Treats:pediatrics with high-risk neuroblastoma
Indications and Usage:16 Unituxin is a GD2-binding monoclonal antibody indicated, incombination with granulocyte-macrophage colony-stimulating factor(GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for thetreatment of pediatric patients with high-risk neuroblastoma whoachieve at least a partial response to prior first-line multiagent,multimodality therapy. (1)
DrugBank Targets:14 1. Ganglioside GD2
Mechanism of Action:16 
Target: GD2
Action: inducer of cell lysis through ADCC and CDC
FDA: Dinutuximab binds to the glycolipid GD2. This glycolipid is expressed on neuroblastoma cellsand on normal cells of neuroectodermal origin, including the central nervous system andperipheral nerves. Dinutuximab binds to cell surface GD2 and induces cell lysis of GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity (ADCC) andcomplement-dependent cytotoxicity (CDC).
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Valchlor16 MECHLORETHAMINE HYDROCHLORIDE Ceptaris Therapeutics August 2013
FDA Label: Valchlor
Disease/s that Drug Treats:Stage IA/IB mycosisfungoides-type cutaneous T-cell lymphoma
Indications and Usage:16 VALCHLOR is an alkylating drug indicated for the topical treatmentof Stage IA and IB mycosis fungoides‐type cutaneous T‐celllymphoma in patients who have received prior skin‐directed therapy(1).  
DrugBank Targets:14 1. DNA
Mechanism of Action:16 
Target: rapidly-proliferating cells
Action: inhibitor
FDA: Mechlorethamine, also known as nitrogen mustard, is an alkylating agent which inhibits rapidly proliferating cells.
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Valstar16 VALRUBICIN Anthra Pharmaceuticals October 1998
FDA Label: Valstar
Disease/s that Drug Treats:Bladder Cancer
Indications and Usage:16 VALSTAR is indicated for intravesical therapy of BCG-refractory carcinoma in situ (CIS) of theurinary bladder in patients for whom immediate cystectomy would be associated withunacceptable morbidity or mortality.
DrugBank Targets:14 1. DNA;2. DNA topoisomerase 2-alpha
Mechanism of Action:16 
Target: DNA topoisomerase II
Action: interferes with normal breaking-resealing action
FDA: Valrubicin is an anthracycline that affects a variety of inter-relatedbiological functions, most of which involve nucleic acid metabolism. It readily penetrates intocells, where it inhibits the incorporation of nucleosides into nucleic acids, causes extensivechromosomal damage, and arrests cell cycle in G2. Although valrubicin does not bind strongly toDNA, a principal mechanism of its action, mediated by valrubicin metabolites, is interferencewith the normal DNA breaking-resealing action of DNA topoisomerase II.
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Vandetanib16 42 vandetanib AstraZeneca April 2011
FDA Label: -
Disease/s that Drug Treats:thyroid cancer
Indications and Usage:16 -
DrugBank Targets:14 1. Vascular endothelial growth factor A;2. Epidermal growth factor receptor;3. Protein-tyrosine kinase 6;4. Angiopoietin-1 receptor
Mechanism of Action:16 
Target: tyrosine kinases
Action: inhibitor
FDA: -
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Vectibix16 42 PANITUMUMAB Amgen September 2006
FDA Label: Vectibix
Disease/s that Drug Treats:colorectal cancer
Indications and Usage:16 Vectibix is an epidermal growth factor receptor (EGFR) antagonist indicatedfor the treatment of wild-type KRAS (exon 2) metastatic colorectal cancer(mCRC) as determined by an FDA-approved test for this use: In combination with FOLFOX for first-line treatment. (1.1, 14.2) As monotherapy following disease progression after prior treatment withfluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy.(1.1, 14.1) Limitation of Use: Vectibix is not indicated for the treatment of patientswith RAS-mutant mCRC or for whom RAS mutation status is unknown.(1.1, 2.1, 5.2, 12.1)
DrugBank Targets:14 1. Epidermal growth factor receptor
Mechanism of Action:16 
Target: EGFR
Action: inhibitor of ligand binding
FDA: The EGFR is a transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine kinases,including EGFR, HER2, HER3, and HER4. EGFR is constitutively expressed in normal epithelial tissues,including the skin and hair follicle. EGFR is overexpressed in certain human cancers, including colon and rectumcancers. Interaction of EGFR with its normal ligands (eg, EGF, transforming growth factor-alpha) leads tophosphorylation and activation of a series of intracellular proteins, which in turn regulate transcription of genesinvolved with cellular growth and survival, motility, and proliferation. KRAS (Kirsten rat sarcoma 2 viraloncogene homologue) and NRAS (Neuroblastoma RAS viral oncogene homologue) are highly related members ofthe RAS oncogene family. Signal transduction through the EGFR can result in activation of the wild-type KRASand NRAS proteins; however, in cells with activating RAS somatic mutations, the RAS-mutant proteins arecontinuously active and appear independent of EGFR regulation.Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the bindingof ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-inducedreceptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth,induction of apoptosis, decreased proinflammatory cytokine and vascular growth factor production, andinternalization of the EGFR. In vitro assays and in vivo animal studies demonstrate that panitumumab inhibits thegrowth and survival of selected human tumor cell lines expressing EGFR.
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Velcade16 42 BORTEZOMIB Millennium Pharmaceuticals May 2003
FDA Label: Velcade
Disease/s that Drug Treats:Multiple Myeloma
Indications and Usage:16 VELCADE is a proteasome inhibitor indicated for: treatment of patients with multiple myeloma (1.1) treatment of patients with mantle cell lymphoma (1.2)
DrugBank Targets:14 1. 26S proteasome non-ATPase regulatory subunit 2;2. 26S proteasome non-ATPase regulatory subunit 1;3. Proteasome subunit beta type-1;4. Proteasome subunit beta type-5;5. Proteasome subunit beta type-2
Mechanism of Action:16 
Target: 26S proteasome
Action: reversible inhibitor of chymotrypsin-like activity
FDA: Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammaliancells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The ubiquitinproteasomepathway plays an essential role in regulating the intracellular concentration of specific proteins,thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targetedproteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostaticmechanisms can lead to cell death. Experiments have demonstrated that bortezomib is cytotoxic to a variety ofcancer cell types in vitro. Bortezomib causes a delay in tumor growth in vivo in nonclinical tumor models,including multiple myeloma.