FDA approved drugs:
(show top 50)
(show all 148)
| # |
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Drug Name |
Active Ingredient(s) 18
|
Company |
Approval Date |
| 1 |
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Abstral
18
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FENTANYL (citrate) |
ProStrakan |
January 2011 |
Disease/s that Drug Treats:breakthrough cancer pain in opiod-tolerant patients
Indications and Usage:
18
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:
16
1. Mu-type opioid receptor ;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:
18
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.
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| 2 |
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Actiq
18
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FENTANYL (citrate) |
Anesta Corporation |
November 1998 |
Disease/s that Drug Treats:cancer pain
Indications and Usage:
18
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:
16
1. Mu-type opioid receptor ;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:
18
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.
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| 3 |
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Akynzeo
18
49
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NETUPITANT AND PALONOSETRON (hydrochloride) |
Helsinn |
October 2014 |
Disease/s that Drug Treats:chemotherapy-induced nausea and vomiting
Indications and Usage:
18
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:
16
1. Substance-P receptor;2. 5-hydroxytryptamine receptor 3A
Mechanism of Action:
18
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.
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| 4 |
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Alimta
18
49
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PEMETREXED (also Pemetrexed Disodium) |
Eli Lilly |
February 2004 |
Disease/s that Drug Treats:Mesothelioma
Indications and Usage:
18
ALIMTA® is a folate analog metabolic inhibitor indicated for: Locally Advanced or Metastatic Nonsquamous Non-Small CellLung Cancer: Initial treatment in combination with cisplatin. (1.1) Maintenance treatment of patients whose disease has notprogressed after four cycles of platinum-based first-linechemotherapy. (1.2) After prior chemotherapy as a single-agent. (1.3) Mesothelioma: in combination with cisplatin. (1.4)Limitations of Use: ALIMTA is not indicated for the treatment of patients withsquamous cell non-small cell lung cancer. (1.5)
DrugBank Targets:
16
1. Thymidylate synthase;2. Bifunctional purine biosynthesis protein PURH;3. Dihydrofolate reductase;4. Trifunctional purine biosynthetic protein adenosine-3
Mechanism of Action:
18
Target: folic acid/ thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase
Action: antagonist/ inhibitor
FDA: ALIMTA, pemetrexed for injection, is a folate analog metabolic inhibitor that exerts its action by disrupting folatedependentmetabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibitsthymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT),which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides.Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate bindingprotein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzymefolylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT.Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, is thought to occur to alesser extent, in normal tissues. Polyglutamated metabolites are thought to have an increased intracellular half-liferesulting in prolonged drug action in malignant cells.
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| 5 |
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Aloxi
18
49
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PALONOSETRON (hydrochloride) |
MGI Pharma, Helsinn Healthcare |
August 2003 |
Disease/s that Drug Treats:Chemotherapy side effects
Indications and Usage:
18
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:
16
5-hydroxytryptamine receptor 3A
Mechanism of Action:
18
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.
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| 6 |
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Aromasin Tablets
18
49
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EXEMESTANE |
Pharmacia & Upjohn |
October 21. 1999 |
Disease/s that Drug Treats:advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy
Indications and Usage:
18
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:
16
Cytochrome P450 19A1
Mechanism of Action:
18
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 âsuicide inhibition.âExemestane 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.
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| 7 |
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Arranon
18
49
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NELARABINE |
GlaxoSmithKline |
October 2005 |
Disease/s that Drug Treats:Lymphoblastic Leukemia
Indications and Usage:
18
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)
Mechanism of Action:
18
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 5â-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.
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| 8 |
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Arzerra
18
49
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OFATUMUMAB |
GlaxoSmithKline |
October 2009 |
Disease/s that Drug Treats:chronic lymphocytic leukemia
Indications and Usage:
18
ARZERRA (ofatumumab) is a CD20-directed cytolytic monoclonal antibodyindicated: in combination with chlorambucil, for the treatment of previouslyuntreated patients with chronic lymphocytic leukemia (CLL) for whomfludarabine-based therapy is considered inappropriate. (1.1) for the treatment of patients with CLL refractory to fludarabine andalemtuzumab. (1.2)
DrugBank Targets:
16
no entry
Mechanism of Action:
18
Target: B-cell
Action: promotes lysis
FDA: Ofatumumab binds specifically to both the small and large extracellular loops of the CD20402 molecule. The CD20 molecule is expressed on normal B lymphocytes (pre-B- to mature403 B-lymphocyte) and on B-cell CLL. The CD20 molecule is not shed from the cell surface and is404 not internalized following antibody binding.405406 The Fab domain of ofatumumab binds to the CD20 molecule and the Fc domain mediates407 immune effector functions to result in B-cell lysis in vitro. Data suggest that possible408 mechanisms of cell lysis include complement-dependent cytotoxicity and antibody-dependent,409 cell-mediated cytotoxicity.
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| 9 |
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Beleodaq
18
49
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BELINOSTAT |
Spectrum Pharmaceuticals |
July 2014 |
Disease/s that Drug Treats:relapsed or refractory peripheral T-cell lymphoma
Indications and Usage:
18
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:
16
no entry
Mechanism of Action:
18
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).
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| 10 |
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Blincyto
18
49
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BLINATUMOMAB |
Amgen |
December 2014 |
Disease/s that Drug Treats:Philadelphia chromosome-negative relapsed /refractory B cell precursor acute lymphoblastic leukemia
Indications and Usage:
18
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:
16
1. B-lymphocyte antigen CD19;2. T-cell surface glycoprotein CD3 delta chain
Mechanism of Action:
18
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.
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| 11 |
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Busulfex
18
49
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BUSULFAN |
Orphan Medical |
February 1999 |
Disease/s that Drug Treats:leukemia
Indications and Usage:
18
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)
Mechanism of Action:
18
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.
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| 12 |
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Campath
18
49
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ALEMTUZUMAB |
Berlex Laboratories |
May 2001 |
Disease/s that Drug Treats:Leukemia
Indications and Usage:
18
LEMTRADA is a CD52-directed cytolytic monoclonal antibody indicated dizziness, abdominal pain, flushing, and vomiting. (6.1) for the treatment of patients with relapsing forms of multiple sclerosis(MS).
DrugBank Targets:
16
1. CAMPATH-1 antigen;2. Low affinity immunoglobulin gamma Fc region receptor III-B;3. Complement C1r subcomponent;4. Complement C1q subcomponent subunit A;5. Complement C1q subcomponent subunit B;6. Complement C1q subcomponent subunit C;7. Low affinity immunoglobulin gamma Fc region receptor III-A;8. High affinity immunoglobulin gamma Fc receptor I;9. Low affinity immunoglobulin gamma Fc region receptor II-a;10. Low affinity immunoglobulin gamma Fc region receptor II-b;11. Low affinity immunoglobulin gamma Fc region receptor II-c;;
Mechanism of Action:
18
Target: CD52 antigen
Action: after binding, induces cell lysis
FDA: The precise mechanism by which alemtuzumab exerts its therapeutic effects in multiple490 sclerosis is unknown but is presumed to involve binding to CD52, a cell surface antigen491 present on T and B lymphocytes, and on natural killer cells, monocytes, and492 macrophages. Following cell surface binding to T and B lymphocytes, alemtuzumab493 results in antibody-dependent cellular cytolysis and complement-mediated lysis.
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| 13 |
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Clolar
18
49
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CLOFARABINE |
Genzyme |
December, 2004 |
Disease/s that Drug Treats:Lymphoblastic Leukemia
Indications and Usage:
18
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:
16
1. DNA polymerase alpha catalytic subunit;2. Ribonucleoside-diphosphate reductase large subunit;3. DNA
Mechanism of Action:
18
Target: ribonucleotide reductase
Action: inhibitor
FDA: Clofarabine is sequentially metabolized intracellularly to the 5â-monophosphate metabolite bydeoxycytidine kinase and mono- and di-phospho-kinases to the active 5â-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 5â-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.
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| 14 |
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Cometriq
18
49
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CABOZANTINIB S-MALATE |
Exelixis |
November 2012 |
Disease/s that Drug Treats:thyroid cancer
Indications and Usage:
18
COMETRIQ is a kinase inhibitor indicated for the treatment ofpatients with progressive, metastatic medullary thyroid cancer(MTC). (1)
DrugBank Targets:
16
1. Hepatocyte growth factor receptor;2. Vascular endothelial growth factor receptor 2;3. Proto-oncogene tyrosine-protein kinase receptor Ret
Mechanism of Action:
18
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.
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| 15 |
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Elitek
18
49
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RASBURICASE |
sanofi-aventis |
October 2009 |
Disease/s that Drug Treats:management of plasma uric acid levels in adults with malignancies
Indications and Usage:
18
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:
16
1. Uric acid
Mechanism of Action:
18
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).
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| 16 |
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Emend
18
49
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APREPITANT FOSAPREPITANT DIMEGLUMINE |
Merck |
March 2003 |
Disease/s that Drug Treats:Chemotherapy-induced Nausea and Vomiting
Indications and Usage:
18
EMEND® is a substance P/neurokinin 1 (NK1) receptor antagonist,indicated: in combination with other antiemetic agents for the:o prevention of acute and delayed nausea and vomitingassociated with initial and repeat courses of highly emetogeniccancer chemotherapy (HEC) including high-dose cisplatin (1.1)o prevention of nausea and vomiting associated with initial andrepeat courses of moderately emetogenic cancer chemotherapy(MEC) (1.1) for the prevention of postoperative nausea and vomiting (PONV)(1.2)Limitations of Use (1.3) Not studied for the treatment of established nausea and vomiting. Chronic continuous administration is not recommended.
DrugBank Targets:
16
1. Substance-P receptor
Mechanism of Action:
18
Target: emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin
Action: inhibitor
FDA: Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors.Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targetsof existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nauseaand vomiting (PONV).Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxicchemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron EmissionTomography (PET) studies with aprepitant have shown that it crosses the blood brain barrier and occupiesbrain NK1 receptors. Animal and human studies show that aprepitant augments the antiemetic activity ofthe 5-HT3-receptor antagonist ondansetron and the corticosteroid dexamethasone and inhibits both theacute and delayed phases of cisplatin-induced emesis.
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| 17 |
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Erbitux
18
49
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CETUXIMAB |
Imclone, Bristol-Myers Squibb |
February 2004 |
Disease/s that Drug Treats:Colorectal Cancer
Indications and Usage:
18
Erbitux® is an epidermal growth factor receptor (EGFR) antagonist indicatedfor treatment of:Head and Neck Cancer Locally or regionally advanced squamous cell carcinoma of the headand neck in combination with radiation therapy. (1.1, 14.1) Recurrent locoregional disease or metastatic squamous cell carcinomaof the head and neck in combination with platinum-based therapy with5-FU. (1.1, 14.1) Recurrent or metastatic squamous cell carcinoma of the head and neckprogressing after platinum-based therapy. (1.1, 14.1)Colorectal CancerK-Ras wild-type, EGFR-expressing, metastatic colorectal cancer asdetermined by FDA-approved tests in combination with FOLFIRI for first-line treatment, in combination with irinotecan in patients who are refractory toirinotecan-based chemotherapy, as a single agent in patients who have failed oxaliplatin- andirinotecan-based chemotherapy or who are intolerant to irinotecan.(1.2, 5.7, 12.1, 14.2)Limitation of Use: Erbitux is not indicated for treatment of Ras-mutantcolorectal cancer. (5.7, 14.2)
DrugBank Targets:
16
1. Epidermal growth factor receptor;2. Low affinity immunoglobulin gamma Fc region receptor III-B;3. Complement C1r subcomponent;4. Complement C1q subcomponent subunit A;5. Complement C1q subcomponent subunit B;6. Complement C1q subcomponent subunit C;7. Low affinity immunoglobulin gamma Fc region receptor III-A;8. Complement C1s subcomponent;9. High affinity immunoglobulin gamma Fc receptor I;10. Low affinity immunoglobulin gamma Fc region receptor II-a;11. Low affinity immunoglobulin gamma Fc region receptor II-b;12. Low affinity immunoglobulin gamma Fc region receptor II-c
Mechanism of Action:
18
Target: binding of epidermal growth factor (EGF) and other ligands to epidermal growth factor receptor (EGFR, HER1, c-ErbB-1)
Action: inhibitor
FDA: The epidermal growth factor receptor (EGFR, HER1, c-ErbB-1) is a transmembraneglycoprotein that is a member of a subfamily of type I receptor tyrosine kinases including EGFR,HER2, HER3, and HER4. The EGFR is constitutively expressed in many normal epithelialtissues, including the skin and hair follicle. Expression of EGFR is also detected in many humancancers including those of the head and neck, colon, and rectum. Cetuximab binds specifically to the EGFR on both normal and tumor cells, and competitivelyinhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforminggrowth factor-alpha. In vitro assays and in vivo animal studies have shown that binding ofcetuximab to the EGFR blocks phosphorylation and activation of receptor-associated kinases,resulting in inhibition of cell growth, induction of apoptosis, and decreased matrixmetalloproteinase and vascular endothelial growth factor production. Signal transduction throughthe EGFR results in activation of wild-type Ras proteins, but in cells with activating Ras somaticmutations, the resulting mutant Ras proteins are continuously active regardless of EGFRregulation.In vitro, cetuximab can mediate antibody-dependent cellular cytotoxicity (ADCC) against certainhuman tumor types. In vitro assays and in vivo animal studies have shown that cetuximabinhibits the growth and survival of tumor cells that express the EGFR. No anti-tumor effects ofcetuximab were observed in human tumor xenografts lacking EGFR expression. The addition ofcetuximab to radiation therapy or irinotecan in human tumor xenograft models in mice resultedin an increase in anti-tumor effects compared to radiation therapy or chemotherapy alone.
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| 18 |
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Erwinaze
18
49
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asparaginase Erwinia chrysanthemi |
Eusa Pharma |
November of 2011 |
Disease/s that Drug Treats:acute lymphoblastic leukemia
Indications and Usage:
18
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:
-
Mechanism of Action:
18
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.
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| 19 |
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Ethyol
18
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AMIFOSTINE |
Alza |
December 8, 1995 |
Disease/s that Drug Treats:ovarian cancer
Indications and Usage:
18
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:
16
1. Ectonucleotide pyrophosphatase/phosphodiesterase family member 1;2. Alkaline phosphatase, placental-like
Mechanism of Action:
18
Target: -
Action: -
FDA: -
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| 20 |
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Eulexin
18
|
FLUTAMIDE |
Schering-Plough |
June 1996 |
Disease/s that Drug Treats:prostate cancer
Indications and Usage:
18
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:
16
1. Androgen receptor;2. Aryl hydrocarbon receptor
Mechanism of Action:
18
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.
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| 21 |
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Evista
18
49
|
RALOXIFENE HYDROCHLORIDE |
Eli Lilly |
September 2007 |
Disease/s that Drug Treats:osteoporosis and reduction of breast cancer risk in postmenopausal women
Indications and Usage:
18
EVISTA is an estrogen agonist/antagonist indicated for Treatment and prevention of osteoporosis in postmenopausal women.(1.1)
DrugBank Targets:
16
1. Estrogen receptor;2. Estrogen receptor beta
Mechanism of Action:
18
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.
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| 22 |
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Farydak
18
49
|
PANOBINOSTAT LACTATE |
Novartis |
February 2015 |
Disease/s that Drug Treats:Multiple myeloma
Indications and Usage:
18
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:
18
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.
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| 23 |
|
Faslodex
18
49
|
FULVESTRANT |
AstraZeneca |
April 2002 |
Disease/s that Drug Treats:Hormone receptor positive metastatic breast cancer
Indications and Usage:
18
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:
16
1. Estrogen receptor
Mechanism of Action:
18
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.
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| 24 |
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Femara
18
49
|
LETROZOLE |
Novartis |
January 2001 |
Disease/s that Drug Treats:Hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer
Indications and Usage:
18
Femara is an aromatase inhibitor indicated for: Adjuva nt treatment of postmenopausal women with hormone receptorpositive early brea st cancer (1.1) Extended adjuvant treatment of postmenopausal women with early brea stcancer who have received prior standard adju vant ta moxifen thera py (1.2) First a nd second-line treatment of postmenopausal women with hormonereceptor positive or unknown advanced breast cancer (1.3)
DrugBank Targets:
16
1. Cytochrome P450 19A1
Mechanism of Action:
18
Target: aromatase enzyme system
Action: inhibitor
FDA: The growth of some cancers of the breast is stimulated or maintained by estrogens. Treatment of breastcancer thought to be hormonally responsive (i.e., estrogen and/or progesterone receptor positive orreceptor unknown) has included a variety of efforts to decrease estrogen levels (ovariectomy,adrenalectomy, hypophysectomy) or inhibit estrogen effects (antiestrogens and progestational agents).These interventions lead to decreased tumor mass or delayed progression of tumor growth in somewomen.In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, whichconverts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. Thesuppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore beachieved by specifically inhibiting the aromatase enzyme.Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits theconversion of androgens to estrogens. In adult nontumor- and tumor-bearing female animals, letrozole isas effective as ovariectomy in reducing uterine weight, elevating serum LH, and causing the regression ofestrogen-dependent tumors. In contrast to ovariectomy, treatment with letrozole does not lead to anincrease in serum FSH. Letrozole selectively inhibits gonadal steroidogenesis but has no significant effecton adrenal mineralocorticoid or glucocorticoid synthesis.Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues. Treatment of womenwith letrozole significantly lowers serum estrone, estradiol and estrone sulfate and has not been shown tosignificantly affect adrenal corticosteroid synthesis, aldosterone synthesis, or synthesis of thyroidhormones.
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| 25 |
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Folotyn
18
49
|
PRALATREXATE |
Allos Therapeutics |
September 2009 |
Disease/s that Drug Treats:peripheral T-cell lymphoma
Indications and Usage:
18
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:
16
1. Dihydrofolate reductase;2. Thymidylate synthase
Mechanism of Action:
18
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.
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| 26 |
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Gardasil
18
49
|
quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine |
Merck |
June 2006 |
Disease/s that Drug Treats:Cervical Cancer Caused by Human Papillomavirus
Indications and Usage:
18
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:
18
Target: humoral immune response
Action: inducer
FDA: HPV only infects human beings. Animal studies with analogous animal papillomaviruses suggest thatthe efficacy of L1 VLP vaccines may involve the development of humoral immune responses. Humanbeings develop a humoral immune response to the vaccine, although the exact mechanism of protectionis unknown.
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| 27 |
|
Gazyva
18
49
|
OBINUTUZUMAB |
Genentech |
October of 2013 |
Disease/s that Drug Treats:previously untreated chronic lymphocytic leukemia
Indications and Usage:
18
GAZYVA (obinutuzumab) is a CD20-directed cytolytic antibody and isindicated, in combination with chlorambucil, for the treatment of patients withpreviously untreated chronic lymphocytic leukemia. (1, 14)
DrugBank Targets:
16
1. B-lymphocyte antigen CD20
Mechanism of Action:
18
Target: CD20 antigen expressed on the surface of pre B- and mature B-lymphocytes
Action: engager of immune cells and/or activator of intracellular death signaling pathways and/or activator of the complement cascade
FDA: Obinutuzumab is a monoclonal antibody that targets the CD20 antigen expressed on the surfaceof pre B- and mature B-lymphocytes. Upon binding to CD20, obinutuzumab mediates B-celllysis through (1) engagement of immune effector cells, (2) by directly activating intracellulardeath signaling pathways and/or (3) activation of the complement cascade. The immune effectorcell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependentcellular phagocytosis.
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| 28 |
|
Gilotrif
18
49
|
AFATINIB DIMALEATE |
Boehringer Ingelheim |
July 2013 |
Disease/s that Drug Treats:metastatic non-small cell lung cancer with EGFR mutations
Indications and Usage:
18
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:
16
1. Epidermal growth factor receptor;2. Receptor tyrosine-protein kinase erbB-2;3. Receptor tyrosine-protein kinase erbB-4
Mechanism of Action:
18
Target: tyrosine kinase autophosphorylation
Action: inhibitor
FDA: Afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) andirreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling.Afatinib demonstrated inhibition of autophosphorylation and in vitro proliferation of cell lines expressing wildtypeEGFR or those expressing selected EGFR exon 19 deletion mutations or exon 21 L858R mutations,including some with a secondary T790M mutation, at afatinib concentrations achieved, at least transiently, inpatients. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2.Treatment with afatinib resulted in inhibition of tumor growth in nude mice implanted with tumors eitheroverexpressing wild type EGFR or HER2 or in an EGFR L858R/T790M double mutant model.
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| 29 |
|
Gliadel Wafer
18
49
|
CARMUSTINE |
Rhone-Poulenc Rorer, Guilford Pharmaceuticals |
February 1997 |
Disease/s that Drug Treats:brain cancer
Indications and Usage:
18
GLIADELWaferisanalkylatingdrugindicatedforthetreatmentof: newly-diagnosedhigh-grade-malignantgliomaasanadjuncttosurgeryandradiation(1)and recurrentglioblastomamultiformeasanadjuncttosurgery(1)
DrugBank Targets:
16
1. Glutathione reductase, mitochondrial;2. DNA;3. RNA
Mechanism of Action:
18
Target: DNA and RNA
Action: alkylating agent
FDA: The activity of GLIADEL Wafer is due to release of cytotoxic concentrations of carmustine, aDNA and RNA alkylating agent, into the tumor resection cavity. On exposure to the aqueousenvironment of the resection cavity, the anhydride bonds in the copolymer are hydrolyzed,releasing carmustine, carboxyphenoxypropane, and sebacic acid into the surrounding braintissue.
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| 30 |
|
Halaven
18
49
|
ERIBULIN MESYLATE |
Eisai |
November 2010 |
Disease/s that Drug Treats:metastatic breast cancer
Indications and Usage:
18
HALAVEN is a microtubule inhibitor indicated for the treatment ofpatients with metastatic breast cancer who have previously receivedat least two chemotherapeutic regimens for the treatment ofmetastatic disease. Prior therapy should have included ananthracycline and a taxane in either the adjuvant or metastaticsetting (1)
DrugBank Targets:
-
Mechanism of Action:
18
Target: microtubule dynamics
Action: inhibitor
FDA: Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesterstubulin into nonproductive aggregates. Eribulin exerts its effects via a tubulin-based antimitoticmechanism leading to G 2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic celldeath after prolonged mitotic blockage
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| 31 |
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Herceptin
18
49
|
TRASTUZUMAB |
Genentech |
October 1998 |
Disease/s that Drug Treats:Breast cancer/gastric cancer
Indications and Usage:
18
Herceptin is a HER2/neu receptor antagonist indicated for: the treatment of HER2 overexpressing breast cancer (1.1, 1.2). the treatment of HER2-overexpressing metastatic gastric orgastroesophageal junction adenocarcinoma (1.3)
DrugBank Targets:
16
1. Receptor tyrosine-protein kinase erbB-2;2. Epidermal growth factor receptor;3. Complement C1r subcomponent;4. Complement C1q subcomponent subunit A;5. Complement C1q subcomponent subunit B;6. Complement C1q subcomponent subunit C;7. Complement C1s subcomponent;8. High affinity immunoglobulin gamma Fc receptor I;9. Low affinity immunoglobulin gamma Fc region receptor II-a;10. Low affinity immunoglobulin gamma Fc region receptor II-b;11. Low affinity immunoglobulin gamma Fc region receptor II-c;12. Low affinity immunoglobulin gamma Fc region receptor III-B;13. Low affinity immunoglobulin gamma Fc region receptor III-A
Mechanism of Action:
18
Target: human epidermal growth factor receptor 2 protein (HER2)
Action: binds with strong affinity for immune response
FDA: The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, which is structurally related to the epidermal growth factor receptor. Herceptin has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2. Herceptin is a mediator of antibody-dependent cellular cytotoxicity (ADCC). In vitro, Herceptin-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.
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| 32 |
|
Hycamtin
18
49
|
TOPOTECAN HYDROCHLORIDE |
GlaxoSmithKline/ SmithKline Beecham |
October 2007/May 1996 |
Disease/s that Drug Treats:small cell lung cancer/ ovarian cancer
Indications and Usage:
18
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:
16
1. DNA topoisomerase 1;2. DNA topoisomerase I, mitochondrial;3. DNA
Mechanism of Action:
18
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.
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| 33 |
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Inform HER-2/neu breast cancer test
18
|
|
Oncor |
January 1998 |
FDA Label: Inform HER-2/neu breast cancer test
Disease/s that Drug Treats:breast cancer prediction
Indications and Usage:
18
DrugBank Targets:
-
Mechanism of Action:
18
Target: -
Action: -
FDA: -
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| 34 |
|
Intron A
18
49
|
INTERFERON ALFA-2B |
Schering-Plough |
December 1997/ December 1995/ March 1997 |
Disease/s that Drug Treats:non-Hodgkin's lymphoma/ malignant melanoma / Hepatitis C
Indications and Usage:
18
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-Hodgkinâs 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-Hodgkinâs 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:
16
1. Interferon alpha/beta receptor 2;2. Interferon alpha/beta receptor 1
Mechanism of Action:
18
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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| 35 |
|
Iressa
18
49
|
GEFITINIB |
AstraZeneca |
May 2003 |
Disease/s that Drug Treats:Non-Small-Cell Lung Cancer
Indications and Usage:
18
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. , IRESSA is indicated as monotherapy for the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies who are benefiting or have benefited from IRESSA. In light of positive survival data with other agents including another oral EGFR inhibitor, physicians should use other treatment options in advanced non-small cell lung cancer patient populations who have received one or two prior chemotherapy regimens and are refractory or intolerant to their most recent regimen. The effectiveness of IRESSA was initially based on objective response rates (see CLINICAL PHARMACOLOGY-Clinical Studies section). Subsequent studies intended to demonstrate an increase in survival have been unsuccessful. Specifically, results from a large placebo-controlled randomized trial in patients with advanced NSCLC who progressed while receiving or within 90 days of the last dose of chemotherapy or were intolerant to the most recent prior chemotherapy regimen, did not show an improvement in survival (see CLINICAL PHARMACOLOGY- Clinical Studies section). Results from two large, controlled, randomized trials in first-line treatment of non-small cell lung cancer showed no benefit from adding IRESSA to doublet, platinum-based chemotherapy.
DrugBank Targets:
16
1. Epidermal growth factor receptor, Epidermal growth factor receptor
Mechanism of Action:
18
Target: EGFR tyrosine kinase and other tyrosine kinases, EGFR tyrosine kinase
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., The mechanism of the clinical antitumor action of gefitinib is not fully characterized. Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (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 receptor expression and response to gefitinib.
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| 36 |
|
Istodax
18
49
|
ROMIDEPSIN |
Gloucester Pharmaceuticals |
November 2009 |
Disease/s that Drug Treats:cutaneous T-cell lymphoma
Indications and Usage:
18
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:
-
Mechanism of Action:
18
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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| 37 |
|
Ixempra
18
49
|
IXABEPILONE |
Bristol-Myers Squibb |
October 2007 |
Disease/s that Drug Treats:Breast cancer
Indications and Usage:
18
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:
16
1. Tubulin beta-3 chain
Mechanism of Action:
18
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.
|
| 38 |
|
Kadcyla
18
49
|
ADO-TRASTUZUMAB EMTANSINE |
Genentech |
February 2013 |
Disease/s that Drug Treats:HER2-positive metastatic breast cancer
Indications and Usage:
18
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:
16
1. Receptor tyrosine-protein kinase erbB-2
Mechanism of Action:
18
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.
|
| 39 |
|
Keytruda
18
49
|
PEMBROLIZUMAB |
Merck |
September 2014 |
Disease/s that Drug Treats:unresectable or metastatic melanoma
Indications and Usage:
18
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:
16
1. Programmed cell death protein 1
Mechanism of Action:
18
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.
|
| 40 |
|
Kyprolis
18
49
|
CARFILZOMIB |
Onyx Pharmaceuticals |
July 2012 |
Disease/s that Drug Treats:multiple myeloma
Indications and Usage:
18
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:
16
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:
18
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.
|
| 41 |
|
Kytril
18
|
GRANISETRON HYDROCHLORIDE |
Roche/SmithKline Beecham |
June 2001/ November 1997 |
Disease/s that Drug Treats:nausea and vomiting associated with chemotherapy
Indications and Usage:
18
KYTRIL Injection is a serotonin-3 (5-HT3) receptor antagonist indicated for: Prevention of nausea and/or vomiting associated with initial and repeatcourses of emetogenic cancer therapy, including high-dose cisplatin. (1) Prevention and treatment of postoperative nausea and vomiting in adults.(1)--------------
DrugBank Targets:
16
1. 5-hydroxytryptamine receptor 3A
Mechanism of Action:
18
Target: 5-hydroxytryptamine3 (5-HT3) receptor
Action: antagonist
FDA: Granisetron is a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist with little or no affinity for otherserotonin receptors, including 5-HT1; 5-HT1A; 5-HT1B/C; 5-HT2; for alpha1-, alpha2- or beta-adrenoreceptors; fordopamine-D2; or for histamine-H1; benzodiazepine; picrotoxin or opioid receptors. Serotonin receptors of the 5-HT3 type are located peripherally on vagal nerve terminals and centrally in thechemoreceptor trigger zone of the area postrema. During chemotherapy-induced vomiting, mucosalenterochromaffin cells release serotonin, which stimulates 5-HT3 receptors. This evokes vagal afferentdischarge and may induce vomiting. Animal studies demonstrate that, in binding to 5-HT3 receptors, granisetronblocks serotonin stimulation and subsequent vomiting after emetogenic stimuli such as cisplatin. In the ferretanimal model, a single granisetron injection prevented vomiting due to high-dose cisplatin or arrested vomitingwithin 5 to 30 seconds.In most human studies, granisetron has had little effect on blood pressure, heart rate or ECG. No evidence of aneffect on plasma prolactin or aldosterone concentrations has been found in other studies.KYTRIL Injection exhibited no effect on oro-cecal transit time in normal volunteers given a single intravenousinfusion of 50 mcg/kg or 200 mcg/kg. Single and multiple oral doses slowed colonic transit in normalvolunteers.
|
| 42 |
|
Lazanda
18
|
FENTANYL CITRATE |
Archimedes |
June 2011 |
Disease/s that Drug Treats:breakthrough cancer pain
Indications and Usage:
18
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:
16
1. Mu-type opioid receptor;2. Delta-type opioid receptor;3. Kappa-type opioid receptor
Mechanism of Action:
18
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.
|
| 43 |
|
Leukine
18
|
SARGRAMOSTIM |
Immunex |
on November 24, 1995/ November 1996 |
Disease/s that Drug Treats:transplantation/ replenishment of white blood cells, fungal infections
Indications and Usage:
18
DrugBank Targets:
16
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:
18
Target: -
Action: -
FDA: -
|
| 44 |
|
Marqibo
18
49
|
VINCRISTINE SULFATE |
Talon Therapeutics |
August 2012 |
Disease/s that Drug Treats:Ph- acute lymphoblastic leukemia
Indications and Usage:
18
Marqibo is a vinca alkaloid indicated for the treatment of adult patients withPhiladelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL)in second or greater relapse or whose disease has progressed following two ormore anti-leukemia therapies. This indication is based on overall responserate. Clinical benefit such as improvement in overall survival has not beenverified (1.1).
DrugBank Targets:
16
1. Tubulin beta chain;2. Tubulin alpha-4A chain
Mechanism of Action:
18
Target: tubulin
Action: alters polymerization equilibrium
FDA: Marqibo is a sphingomyelin/cholesterol liposome-encapsulated formulation of vincristine sulfate.Non-liposomal vincristine sulfate binds to tubulin, altering the tubulin polymerization equilibrium, resulting inaltered microtubule structure and function. Non-liposomal vincristine sulfate stabilizes the spindle apparatus,preventing chromosome segregation, triggering metaphase arrest and inhibition of mitosis.
|
| 45 |
|
Miraluma Test
18
|
TECHNETIUM TC-99M SESTAMIBI KIT |
DuPont Merck Pharmaceutical Company |
May 1997 |
Disease/s that Drug Treats:breast imaging
Indications and Usage:
18
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:
18
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.
|
| 46 |
|
Mozobil
18
49
|
PLERIXAFOR |
Genzyme |
December 2008 |
Disease/s that Drug Treats:non-Hodgkinâs lymphoma and multiple myeloma
Indications and Usage:
18
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-Hodgkinâslymphoma and multiple myeloma. (1)
DrugBank Targets:
16
1. C-X-C chemokine receptor type 4
Mechanism of Action:
18
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.
|
| 47 |
|
Mylotarg
18
49
|
GEMTUZUMAB OZOGAMICIN |
Wyeth |
May 2000 |
Disease/s that Drug Treats:Acute Myeloid Leukemia (AML)
Indications and Usage:
18
Mylotarg is indicated for the treatment of patients with CD33 positive acute myeloid leukemia infirst relapse who are 60 years of age or older and who are not considered candidates for othercytotoxic chemotherapy. The safety and efficacy of Mylotarg in patients with poor performancestatus and organ dysfunction has not been established.The effectiveness of Mylotarg is based on OR rates (see CLINICAL STUDIES section). Thereare no controlled trials demonstrating a clinical benefit, such as improvement in disease-relatedsymptoms or increased survival, compared to any other treatment.
DrugBank Targets:
16
1. Myeloid cell surface antigen CD33;2. Low affinity immunoglobulin gamma Fc region receptor III-B;3. Complement C1r subcomponent;4. Complement C1q subcomponent subunit A;5. Complement C1q subcomponent subunit B;6. Complement C1q subcomponent subunit C;7. Low affinity immunoglobulin gamma Fc region receptor III-A;8. Complement C1s subcomponent;9. High affinity immunoglobulin gamma Fc receptor I;10. Low affinity immunoglobulin gamma Fc region receptor II-a;11. Low affinity immunoglobulin gamma Fc region receptor II-b;12. Low affinity immunoglobulin gamma Fc region receptor II-c
Mechanism of Action:
18
Target: CD33 antigen expressed byhematopoietic cells
Action: binds to form complex that then causes a break in the DNA double strand
FDA: Mylotarg is directed against the CD33 antigen expressed byhematopoietic cells. Binding of the anti-CD33 antibody portion of Mylotarg with the CD33antigen results in the formation of a complex that is internalized. Upon internalization, thecalicheamicin derivative is released inside the lysosomes of the myeloid cell. The releasedcalicheamicin derivative binds to DNA in the minor groove resulting in DNA double strandbreaks and cell death.Gemtuzumab ozogamicin is cytotoxic to the CD33 positive HL-60 human leukemia cell line.Gemtuzumab ozogamicin produces significant inhibition of colony formation in cultures of adultleukemic bone marrow cells. The cytotoxic effect on normal myeloid precursors leads tosubstantial myelosuppression, but this is reversible because pluripotent hematopoietic stem cellsare spared. In preclinical animal studies, gemtuzumab ozogamicin demonstrates antitumoreffects in the HL-60 human promyelocytic leukemia xenograft tumor in athymic mice.
|
| 48 |
|
Neulasta
18
|
PEGFILGRASTIM |
Amgen |
January 2002 |
Disease/s that Drug Treats:Neutropenia
Indications and Usage:
18
Neulasta is a man-made form of granulocyte colony-stimulating factor (G-CSF), which is made using the bacteriaEscherichia coli. G-CSF is a substance produced by the body. It stimulates the growth of neutrophils (nu-tro-fils),a type of white blood cell important in the bodyâs fight against infection.
DrugBank Targets:
16
1. Granulocyte colony-stimulating factor receptor;2. Neutrophil elastase
Mechanism of Action:
18
Target: hematopoietic cells
Action: stimulates proliferation
FDA: -
|
| 49 |
|
Nexavar
18
49
|
SORAFENIB TOSYLATE |
Bayer/Onyx |
December 2005 |
Disease/s that Drug Treats:Renal Cell Carcinoma
Indications and Usage:
18
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:
16
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:
18
Target: c-CRAF, BRAF and mutant BRAF, KIT, FLT- 3, RET, RET/PTC, VEGFR-1, VEGFR- 2, VEGFR- 3, and PDGFR-Ã
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-Ã). 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.
|
| 50 |
|
Nolvadex
18
49
|
TAMOXIFEN CITRATE |
AstraZeneca |
October 1998 |
Disease/s that Drug Treats:Breast Cancer
Indications and Usage:
18
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. âHigh riskâ 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:
16
1. Estrogen receptor;2. Estrogen receptor beta;3. 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase;4. Protein kinase C
Mechanism of Action:
18
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.
|
Interventional clinical trials:
| # |
Name |
Status |
NCT ID |
Phase |
Drugs |
| 1 |
Biological Significance of the Bloom's Syndrome Protein |
Completed |
NCT00021437
|
|
|
Cochrane evidence based reviews: bloom syndrome
|
Rare skin diseases
