FDA approved drugs:
(show all 34)
| # |
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Drug Name |
Active Ingredient(s) 18
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Company |
Approval Date |
| 1 |
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Afinitor
18
49
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EVEROLIMUS |
Novartis |
March 2009 |
Disease/s that Drug Treats:renal cell carcinoma/ renal angiomyolipoma associated with tuberous sclerosis complex/ advanced pancreatic neuroendocrine tumors/ hormone receptor-positive, HER2-negative breast cancer
Indications and Usage:
18
AFINITOR is a kinase inhibitor indicated for the treatment of: postmenopausal women with advanced hormone receptor-positive, HER2- negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole. (1.1) adults with progressive neuroendocrine tumors of pancreatic origin (PNET) that are unresectable, locally advanced or metastatic. AFINITOR is not indicated for the treatment of patients with functional carcinoid tumors. (1.2) adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. (1.3) adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. The effectiveness of AFINITOR in the treatment of renal angiomyolipoma is based on an analysis of durable objective responses in patients treated for a median of 8.3 months. Further follow-up of patients is required to determine long-term outcomes. (1.4) AFINITOR and AFINITOR DISPERZ are kinase inhibitors indicated for the treatment of: pediatric and adult patients with tuberous sclerosis complex (TSC) who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. The effectiveness is based on demonstration of durable objective response, as evidenced by reduction in SEGA tumor volume. Improvement in diseaserelated symptoms and overall survival in patients with SEGA and TSC has not been demonstrated. (1.5)
DrugBank Targets:
16
Serine/threonine-protein kinase mTOR
Mechanism of Action:
18
Target: mTOR
Action: inhibitor
FDA: Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of thePI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers. Everolimus binds to an intracellularprotein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex 1 (mTORC1) and thus inhibition ofmTOR kinase activity. Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic initiationfactor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis. S6K1 is a substrate ofmTORC1 and phosphorylates the activation domain 1 of the estrogen receptor which results in ligand-independentactivation of the receptor. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) andreduced the expression of vascular endothelial growth factor (VEGF). Inhibition of mTOR by everolimus has been shownto reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies.Constitutive activation of the PI3K/Akt/mTOR pathway can contribute to endocrine resistance in breast cancer. In vitrostudies show that estrogen-dependent and HER2+ breast cancer cells are sensitive to the inhibitory effects of everolimus,and that combination treatment with everolimus and Akt, HER2, or aromatase inhibitors enhances the anti-tumor activityof everolimus in a synergistic manner.Two regulators of mTORC1 signaling are the oncogene suppressors tuberin-sclerosis complexes 1 and 2 (TSC1, TSC2).Loss or inactivation of either TSC1 or TSC2 leads to activation of downstream signaling. In TSC, a genetic disorder,inactivating mutations in either the TSC1 or the TSC2 gene lead to hamartoma formation throughout the body.
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| 2 |
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Bexxar
18
49
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TOSITUMOMAB; IODINE I 131 TOSITUMOMAB |
Corixa |
June 2003 |
Disease/s that Drug Treats:Non-Hodgkin's Lymphoma
Indications and Usage:
18
BEXXAR (tositumomab and Iodine I 131 tositumomab) is a CD20-directedradiotherapeutic antibody indicated for the treatment of patients with CD20-positive, relapsed or refractory, low-grade, follicular, or transformed nonHodgkin'slymphoma who have progressed during or after rituximab therapy,including patients with rituximab-refractory non-Hodgkin's lymphoma. (1.1)Determination of the effectiveness of the BEXXAR therapeutic regimen isbased on overall response rates in patients whose disease is refractory tochemotherapy and rituximab. The effects of the BEXXAR therapeuticregimen on survival are not known. (1.1)Important Limitation of Use BEXXAR therapeutic regimen is only indicated for a single course oftreatment and is not indicated for a first-line treatment. (1.2)
DrugBank Targets:
16
1. B-lymphocyte antigen CD20;2. Low affinity immunoglobulin gamma Fc region receptor III-B;3. Complement C1r subcomponent;4. Complement C1q subcomponent subunit A;5. Complement C1q subcomponent subunit B;6. Complement C1q subcomponent subunit C;7. Low affinity immunoglobulin gamma Fc region receptor III-A;8. High affinity immunoglobulin gamma Fc receptor I;9. Low affinity immunoglobulin gamma Fc region receptor II-a;10.Low affinity immunoglobulin gamma Fc region receptor II-b;11. Low affinity immunoglobulin gamma Fc region receptor II-c
Mechanism of Action:
18
Target: CD20
Action: cytotoxic antibody
FDA: Tositumomab binds specifically to an epitope within the extracellular domain of the586 CD20 molecule. The CD20 molecule is expressed on normal B lymphocytes (pre-B lymphocytes587 to mature B lymphocytes) and on B-cell non-Hodgkin's lymphomas. The CD20 molecule is not588 shed from the cell surface and is not internalized following antibody binding. The BEXXAR589 therapeutic regimen induces cell death by emitting ionizing radiation to CD20-expressing590 lymphocytes or neighboring cells. In addition to cell death mediated by the radioisotope, other591 possible mechanisms of action include antibody-dependent cellular cytotoxicity, complement-592 dependent cytotoxicity, and CD20-mediated apoptosis.
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| 3 |
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Bosulif
18
49
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BOSUTINIB MONOHYDRATE |
Pfizer |
September 2012 |
Disease/s that Drug Treats:Ph+ chronic myelogenous leukemia
Indications and Usage:
18
BOSULIF is a kinase inhibitor indicated for the treatment of adult patientswith chronic, accelerated, or blast phase Ph+ chronic myelogenous leukemia(CML) with resistance or intolerance to prior therapy. (1)
DrugBank Targets:
16
1. Breakpoint cluster region protein;2. Tyrosine-protein kinase ABL1;3. Tyrosine-protein kinase Lyn;4. Tyrosine-protein kinase HCK;5. Proto-oncogene tyrosine-protein kinase Src;6. Cyclin-dependent kinase 2;7. Dual specificity mitogen-activated protein kinase kinase 1;8. Dual specificity mitogen-activated protein kinase kinase 2;9. Mitogen-activated protein kinase kinase kinase 2;10. Calcium/calmodulin-dependent protein kinase type II subunit gamma
Mechanism of Action:
18
Target: tyrosine kinase/ Src-family kinases including Src, Lyn, and Hck
Action: inhibitor
FDA: Bosutinib is a tyrosine kinase inhibitor. Bosutinib inhibits the Bcr-Abl kinase that promotes CML; it is also aninhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms ofBcr-Abl expressed in murine myeloid cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells. In mice,treatment with bosutinib reduced the size of CML tumors relative to controls and inhibited growth of murine myeloidtumors expressing several imatinib-resistant forms of Bcr-Abl.
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| 4 |
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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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| 5 |
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Degarelix
18
49
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degarelix |
Ferring Pharmaceuticals |
December of 2008 |
Disease/s that Drug Treats:Prostate Cancer
Indications and Usage:
18
DrugBank Targets:
16
1. Gonadotropin-releasing hormone receptor
Mechanism of Action:
18
Target: Gonadotropin-releasing hormone (GnRH) receptor
Action: antagonist
FDA: -
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| 6 |
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Ellence
18
49
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EPIRUBICIN HYDROCHLORIDE |
Pharmacia & Upjohn |
September 1999 |
Disease/s that Drug Treats:Component of adjuvant therapy in patients with evidence of axillary node tumor involvement for primary breast cancer
Indications and Usage:
18
ELLENCE Injection is an anthracycline topoisomerase II inhibitor indicatedas a component of adjuvant therapy in patients with evidence of axillary nodetumor involvement following resection of primary breast cancer (1).
DrugBank Targets:
16
1. Chromodomain-helicase-DNA-binding protein 1;2. DNA topoisomerase 2-alpha;3. DNA
Mechanism of Action:
18
Target: nucleic acid (DNA and RNA) and protein synthesis
Action: inhibitor
FDA: Epirubicin is an anthracycline cytotoxic agent. Although it is known that anthracyclines can interfere with a number of biochemical andbiological functions within eukaryotic cells, the precise mechanisms of epirubicinâs cytotoxic and/or antiproliferative properties have not beencompletely elucidated.Epirubicin forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs, with consequent inhibition of nucleicacid (DNA and RNA) and protein synthesis.Such intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Epirubicin also inhibits DNA helicase activity,preventing the enzymatic separation of double-stranded DNA and interfering with replication and transcription. Epirubicin is also involved inoxidation/reduction reactions by generating cytotoxic free radicals. The antiproliferative and cytotoxic activity of epirubicin is thought to resultfrom these or other possible mechanisms.Epirubicin is cytotoxic in vitro to a variety of established murine and human cell lines and primary cultures of human tumors. It is also activein vivo against a variety of murine tumors and human xenografts in athymic mice, including breast tumors.
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| 7 |
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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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| 8 |
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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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| 9 |
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Evista
18
49
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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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| 10 |
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Femara
18
49
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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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| 11 |
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Gardasil
18
49
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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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| 12 |
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Mozobil
18
49
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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.
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| 13 |
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Nexavar
18
49
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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.
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| 14 |
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Sancuso
18
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GRANISETRON |
ProStrakan |
September 2008 |
Disease/s that Drug Treats:chemotherapy-induced nausea and vomiting
Indications and Usage:
18
Sancuso is a serotonin subtype 3 (5-HT3) receptor antagonist indicated for theprevention of nausea and vomiting in patients receiving moderately and/orhighly emetogenic chemotherapy for up to 5 consecutive days. (1)
DrugBank Targets:
16
1. 5-hydroxytryptamine receptor 3A
Mechanism of Action:
18
Target: 5-hydroxytryptamine3 (5-HT3) receptor
Action: agonist
FDA: Granisetron is a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist with little or no affinityfor other serotonin receptors, including 5-HT1, 5-HT1A, 5-HT1B/C, 5-HT2; for alpha1-, alpha2-, or betaadrenoreceptors;for dopamine-D2; or for histamine-H1; benzodiazepine; picrotoxin or opioidreceptors.Serotonin receptors of the 5-HT3 type are located peripherally on vagal nerve terminals and centrallyin the chemoreceptor trigger zone of the area postrema. During chemotherapy that inducesvomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HT3 receptors. Thisevokes vagal afferent discharge, inducing vomiting. Animal studies demonstrate that, in binding to5-HT3 receptors, granisetron blocks serotonin stimulation and subsequent vomiting after emetogenicstimuli such as cisplatin. In the ferret animal model, a single granisetron injection preventedvomiting due to high-dose cisplatin or arrested vomiting within 5 to 30 seconds.
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| 15 |
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Sprycel
18
49
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DASATINIB |
Bristol-Myers Squibb |
June 2006 |
Disease/s that Drug Treats:Chronic Myeloid Leukemia
Indications and Usage:
18
SPRYCEL is a kinase inhibitor indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+)chronic myeloid leukemia (CML) in chronic phase. (1, 14) adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+CML with resistance or intolerance to prior therapy including imatinib. (1,14) adults with Philadelphia chromosome-positive acute lymphoblasticleukemia (Ph+ ALL) with resistance or intolerance to prior therapy. (1, 14)
DrugBank Targets:
16
1. Tyrosine-protein kinase ABL1;2. Proto-oncogene tyrosine-protein kinase Src;3. Ephrin type-A receptor 2;4. Tyrosine-protein kinase Lck;5. Tyrosine-protein kinase Yes;6. Mast/stem cell growth factor receptor Kit;7. Platelet-derived growth factor receptor beta;8. Signal transducer and activator of transcription 5B;9. Abelson tyrosine-protein kinase 2;10. Tyrosine-protein kinase Fyn
Mechanism of Action:
18
Target: BCR-ABL, SRC family(SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ kinases
Action: inhibitor
FDA: Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family(SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib ispredicted to bind to multiple conformations of the ABL kinase.In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylatesensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia(CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under theconditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCRABLkinase domain mutations, activation of alternate signaling pathways involving the SRCfamily kinases (LYN, HCK), and multi-drug resistance gene overexpression.
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| 16 |
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Sutent
18
49
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SUNITINIB MALATE |
Pfizer |
May 2011/ January 2006 |
Disease/s that Drug Treats:pancreatic neuroendocrine tumors/ Kidney Cancer/Gastrointestinal Stromal Tumors
Indications and Usage:
18
SUTENT is a kinase inhibitor indicated for the treatment of: Gastrointestinal stromal tumor (GIST) after disease progression on orintolerance to imatinib mesylate. (1.1) Advanced renal cell carcinoma (RCC). (1.2) Progressive, well-differentiated pancreatic neuroendocrine tumors(pNET) in patients with unresectable locally advanced or metastaticdisease. (1.3)
DrugBank Targets:
16
1. Platelet-derived growth factor receptor beta;2. Vascular endothelial growth factor receptor 1;3. Mast/stem cell growth factor receptor Kit;4. Vascular endothelial growth factor receptor 2;5. Vascular endothelial growth factor receptor 3;6. Receptor-type tyrosine-protein kinase FLT3;7. Macrophage colony-stimulating factor 1 receptor;8. Platelet-derived growth factor receptor alpha
Mechanism of Action:
18
Target: variety of kinases, platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factorreceptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3(FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factorreceptor (RET)
Action: inhibitor
FDA: Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), some of which areimplicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib wasevaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitorof platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factorreceptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3(FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factorreceptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical andcellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primarymetabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.Sunitinib inhibited the phosphorylation of multiple RTKs (PDGFRï¢, VEGFR2, KIT) in tumor xenograftsexpressing RTK targets in vivo and demonstrated inhibition of tumor growth or tumor regression and/orinhibited metastases in some experimental models of cancer. Sunitinib demonstrated the ability to inhibitgrowth of tumor cells expressing dysregulated target RTKs (PDGFR, RET, or KIT) in vitro and to inhibitPDGFRï¢- and VEGFR2-dependent tumor angiogenesis in vivo.
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| 17 |
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Synercid I.V.
18
|
DALFOPRISTIN; QUINUPRISTIN QUINUPRISTIN; DALFOPRISTIN |
Rhone Poulenc Rorer |
September 1999 |
Disease/s that Drug Treats:For serious or life-threatening infections associated w/ vancomycin-resistant Enterococcus faecium (VREF) bacteremia.
Indications and Usage:
18
Synercid is indicated in adults for the treatment of the following infections when caused bysusceptible strains of the designated microorganisms.Complicated skin and skin structure infections caused by Staphylococcus aureus (methicillinsusceptible) or Streptococcus pyogenes. (See CLINICAL STUDIES.)
DrugBank Targets:
16
16
1. Streptogramin A acetyltransferase| 1. 23S rRNA;2. 50S ribosomal protein L10;3. 50S ribosomal protein L22
Mechanism of Action:
18
Target: bacterial ribosome - protien synthesis
Action: inhibitor
FDA: The site of action of quinupristin and dalfopristin is the bacterial ribosome. Dalfopristin has beenshown to inhibit the early phase of protein synthesis while quinupristin inhibits the late phase ofprotein synthesis. Synercid is bactericidal against isolates of methicillin-susceptible andmethicillin-resistant staphylococci. The mode of action of Synercid differs from that of otherclasses of antibacterial agents such as Ã-lactams, aminoglycosides, glycopeptides, quinolones,macrolides, lincosamides and tetracyclines. Therefore, there is no cross resistance betweenSynercid and these agents when tested by the minimum inhibitory concentration (MIC) method.
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| 18 |
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Tasigna
18
49
|
NILOTINIB HYDROCHLORIDE MONOHYDRATE |
Novartis |
October 2007 |
Disease/s that Drug Treats:chronic myelogenous leukemia
Indications and Usage:
18
Tasigna is a kinase inhibitor indicated for:The treatment of newly diagnosed adult patients with Philadelphiachromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase.The treatment of chronic phase (CP) and accelerated phase (AP) Ph+ CML inadult patients resistant to or intolerant to prior therapy that included imatinib.(1.2)--------------
DrugBank Targets:
16
1. Tyrosine-protein kinase ABL1;2. Mast/stem cell growth factor receptor Kit
Mechanism of Action:
18
Target: Bcr-Abl kinase, c-kit and Platelet Derived Growth Factor (PDGF)
Action: inhibitor of signal transduction
FDA: Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation ofthe kinase domain of ABL protein. In vitro, nilotinib inhibited BCR-ABL mediated proliferation of murineleukemic cell lines and human cell lines derived from patients with Ph+ CML. Under the conditions of theassays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 outof 33 mutations tested. In vivo, nilotinib reduced the tumor size in a murine BCR-ABL xenograft model.Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: BCR-ABL (20to 60 nM), PDGFR (69 nM), c-KIT (210 nM), CSF-1R (125 to 250 nM), and DDR1 (3.7 nM).
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| 19 |
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Torisel
18
49
|
TEMSIROLIMUS |
Wyeth |
May 2007 |
Disease/s that Drug Treats:renal cell carcinoma
Indications and Usage:
18
TORISEL® is a kinase inhibitor indicated for the treatment of advanced renalcell carcinoma. (1)
DrugBank Targets:
16
1. Serine/threonine-protein kinase mTOR
Mechanism of Action:
18
Target: mTOR
Action: inhibitor
FDA: Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds toan intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTORthat controls cell division. Inhibition of mTOR activity resulted in a G1 growth arrest in treatedtumor cells. When mTOR was inhibited, its ability to phosphorylate p70S6k and S6 ribosomalprotein, which are downstream of mTOR in the PI3 kinase/AKT pathway was blocked. Inin vitro studies using renal cell carcinoma cell lines, temsirolimus inhibited the activity of mTORand resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha, and thevascular endothelial growth factor.
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| 20 |
|
Tykerb
18
49
|
LAPATINIB DITOSYLATE |
GlaxoSmithKline |
March 2007 |
Disease/s that Drug Treats:breast cancer
Indications and Usage:
18
TYKERB, a kinase inhibitor, is indicated in combination with: (1) capecitabine, for the treatment of patients with advanced or metastatic breastcancer whose tumors overexpress HER2 and who have received prior therapyincluding an anthracycline, a taxane, and trastuzumab.Limitation of Use: Patients should have disease progression on trastuzumabprior to initiation of treatment with TYKERB in combination with capecitabine. letrozole for the treatment of postmenopausal women with hormone receptorpositivemetastatic breast cancer that overexpresses the HER2 receptor forwhom hormonal therapy is indicated.TYKERB in combination with an aromatase inhibitor has not been comparedto a trastuzumab-containing chemotherapy regimen for the treatment ofmetastatic breast cancer.
DrugBank Targets:
16
1. Epidermal growth factor receptor;2. Receptor tyrosine-protein kinase erbB-2
Mechanism of Action:
18
Target: Epidermal Growth Factor Receptor (EGFR [ErbB1]), Human Epidermal Receptor Type 2 (HER-2 [ErbB2]) receptor
Action: inhibitor intracellular tyrosine kinase domains
FDA: Lapatinib is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinasedomains of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and of Human EpidermalReceptor Type 2 (HER2 [ErbB2]) receptors (estimated Kiapp values of 3nM and 13nM,respectively) with a dissociation half-life of ï³300 minutes. Lapatinib inhibits ErbB-driven tumorcell growth in vitro and in various animal models.An additive effect was demonstrated in an in vitro study when lapatinib and 5-FU (theactive metabolite of capecitabine) were used in combination in the 4 tumor cell lines tested. Thegrowth inhibitory effects of lapatinib were evaluated in trastuzumab-conditioned cell lines.Lapatinib retained significant activity against breast cancer cell lines selected for long-termgrowth in trastuzumab-containing medium in vitro. These in vitro findings suggest non-crossresistancebetween these two agents.Hormone receptor-positive breast cancer cells (with ER [Estrogen Receptor] and/or PgR[Progesterone Receptor]) that coexpress the HER2 tend to be resistant to established endocrinetherapies. Similarly, hormone receptor-positive breast cancer cells that initially lack EGFR orHER2 upregulate these receptor proteins as the tumor becomes resistant to endocrine therapy.
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| 21 |
|
Valchlor
18
|
MECHLORETHAMINE HYDROCHLORIDE |
Ceptaris Therapeutics |
August 2013 |
Disease/s that Drug Treats:Stage IA/IB mycosisfungoides-type cutaneous T-cell lymphoma
Indications and Usage:
18
VALCHLOR is an alkylating drug indicated for the topical treatmentof Stage IA and IB mycosis fungoidesâtype cutaneous Tâcelllymphoma in patients who have received prior skinâdirected therapy(1). Â
DrugBank Targets:
16
1. DNA
Mechanism of Action:
18
Target: rapidly-proliferating cells
Action: inhibitor
FDA: Mechlorethamine, also known as nitrogen mustard, is an alkylating agent which inhibits rapidly proliferating cells.
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| 22 |
|
Vectibix
18
49
|
PANITUMUMAB |
Amgen |
September 2006 |
Disease/s that Drug Treats:colorectal cancer
Indications and Usage:
18
Vectibix is an epidermal growth factor receptor (EGFR) antagonist indicatedfor the treatment of wild-type KRAS (exon 2) metastatic colorectal cancer(mCRC) as determined by an FDA-approved test for this use: In combination with FOLFOX for first-line treatment. (1.1, 14.2) As monotherapy following disease progression after prior treatment withfluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy.(1.1, 14.1) Limitation of Use: Vectibix is not indicated for the treatment of patientswith RAS-mutant mCRC or for whom RAS mutation status is unknown.(1.1, 2.1, 5.2, 12.1)
DrugBank Targets:
16
1. Epidermal growth factor receptor
Mechanism of Action:
18
Target: EGFR
Action: inhibitor of ligand binding
FDA: The EGFR is a transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine kinases,including EGFR, HER2, HER3, and HER4. EGFR is constitutively expressed in normal epithelial tissues,including the skin and hair follicle. EGFR is overexpressed in certain human cancers, including colon and rectumcancers. Interaction of EGFR with its normal ligands (eg, EGF, transforming growth factor-alpha) leads tophosphorylation and activation of a series of intracellular proteins, which in turn regulate transcription of genesinvolved with cellular growth and survival, motility, and proliferation. KRAS (Kirsten rat sarcoma 2 viraloncogene homologue) and NRAS (Neuroblastoma RAS viral oncogene homologue) are highly related members ofthe RAS oncogene family. Signal transduction through the EGFR can result in activation of the wild-type KRASand NRAS proteins; however, in cells with activating RAS somatic mutations, the RAS-mutant proteins arecontinuously active and appear independent of EGFR regulation.Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the bindingof ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-inducedreceptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth,induction of apoptosis, decreased proinflammatory cytokine and vascular growth factor production, andinternalization of the EGFR. In vitro assays and in vivo animal studies demonstrate that panitumumab inhibits thegrowth and survival of selected human tumor cell lines expressing EGFR.
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| 23 |
|
Xalkori
18
49
|
CRIZOTINIB |
Pfizer |
August of 2011 |
Disease/s that Drug Treats:ALK+ non-small cell lung cancer
Indications and Usage:
18
XALKORI is a kinase inhibitor indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplasticlymphoma kinase (ALK)-positive as detected by an FDA-approved test. (1), XALKORI is a kinase inhibitor indicated for the treatment of patients with: * metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. (1.1) * metastatic NSCLC whose tumors are ROS1-positive. (1.2)
DrugBank Targets:
16
1. ALK tyrosine kinase receptor;2. Hepatocyte growth factor receptor, ALK tyrosine kinase receptor|Hepatocyte growth factor receptor
Mechanism of Action:
18
Target: receptor tyrosine kinases, receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and Recepteur dâOrigine Nantais (RON)
Action: inhibitor
FDA: Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor(HGFR, c-Met), ROS1 (c-ros), and Recepteur dâOrigine Nantais (RON). Translocations can affect the ALKgene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results inactivation and dysregulation of the geneâs expression and signaling which can contribute to increased cellproliferation and survival in tumors expressing these proteins. Crizotinib demonstrated concentration-dependentinhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines anddemonstrated antitumor activity in mice bearing tumor xenografts that expressed EML4- or NPM-ALK fusionproteins or c-Met. , Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur dâOrigine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the geneâs expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins. Crizotinib demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed echinoderm microtubule-associated protein-like 4 (EML4)- or nucleophosmin (NPM)-ALK fusion proteins or c-Met.
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| 24 |
|
Zuplenz
18
|
ONDANSETRON |
Strativa Pharmaceuticals |
July 2010 |
Disease/s that Drug Treats:post-operative, chemotherapy and radiotherapy induced nausea and vomiting
Indications and Usage:
18
ZUPLENZ is a 5-HT3 receptor antagonist indicated for: Prevention of nausea and vomiting associated with highly emetogenic cancerchemotherapy. (1.1) Prevention of nausea and vomiting associated with initial and repeat coursesof moderately emetogenic cancer chemotherapy. (1.2) Prevention of nausea and vomiting associated with radiotherapy in patientsreceiving total body irradiation, single high-dose fraction to abdomen, ordaily fractions to the abdomen. (1.3) Prevention of postoperative nausea and/or vomiting. (1.4)
DrugBank Targets:
16
1. 5-hydroxytryptamine receptor 3A;2. 5-hydroxytryptamine receptor 4;3. Mu-type opioid receptor;4. 5-hydroxytryptamine receptor 1A;5. 5-hydroxytryptamine receptor 1B
Mechanism of Action:
18
Target: 5-HT3 receptor
Action: selective antagonist
FDA: Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron isnot a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals andcentrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetronâ s antiemetic action is mediatedcentrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from theenterochromaffin cells of the small intestine. In humans, urinary 5-HIAA (5-hydroxyindoleacetic acid) excretion increases aftercisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5-HT3 receptors and initiate the vomiting reflex. In animals, the emetic response to cisplatin can be prevented by pretreatment with aninhibitor of serotonin synthesis, bilateral abdominal vagotomy and greater splanchnic nerve section, or pretreatment with a serotonin5-HT3 receptor antagonist.
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| 25 |
|
Zytiga
18
49
|
ABIRATERONE ACETATE |
Centocor Ortho Biotech |
May 2011 |
Disease/s that Drug Treats:prostate cancer
Indications and Usage:
18
ZYTIGA is a CYP17 inhibitor indicated in combination with prednisone forthe treatment of patients with metastatic castration-resistant prostate cancer.(1)
DrugBank Targets:
16
1. Steroid 17-alpha-hydroxylase/17,20 lyase
Mechanism of Action:
18
Target: 17 α-hydroxylase/C17,20-lyase (CYP17)
Action: inhibitor
FDA: Abiraterone acetate (ZYTIGA) is converted in vivo to abiraterone, an androgen biosynthesisinhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed intesticular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis.CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone andprogesterone to their 17α-hydroxy derivatives by 17α-hydroxylase activity and 2) thesubsequent formation of dehydroepiandrosterone (DHEA) and androstenedione,respectively, by C17, 20 lyase activity. DHEA and androstenedione are androgens and areprecursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increasedmineralocorticoid production by the adrenals [see Warnings and Precautions (5.1)].Androgen sensitive prostatic carcinoma responds to treatment that decreases androgenlevels. Androgen deprivation therapies, such as treatment with GnRH agonists ororchiectomy, decrease androgen production in the testes but do not affect androgenproduction by the adrenals or in the tumor. ZYTIGA decreased serum testosterone and other androgens in patients in theplacebo-controlled Phase 3 clinical trial. It is not necessary to monitor the effect of ZYTIGAon serum testosterone levels.Changes in serum prostate specific antigen (PSA) levels may be observed but have not beenshown to correlate with clinical benefit in individual patients.
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| 26 |
|
Allegra
18
|
FEXOFENADINE HYDROCHLORIDE |
Hoechst Marion Roussel |
July 1996 |
Disease/s that Drug Treats:seasonal allergic rhinitis
Indications and Usage:
18
Seasonal Allergic Rhinitis ALLEGRA is indicated for the relief of symptoms associated with seasonal allergic rhinitis in adults and children 6 years of age and older. Symptoms treated effectively were sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes. Chronic Idiopathic Urticaria ALLEGRA is indicated for treatment of uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 years of age and older. It significantly reduces pruritus and the number of wheals.
DrugBank Targets:
16
Histamine H1 receptor
Mechanism of Action:
18
Target: -
Action: -
FDA: Fexofenadine hydrochloride is an antihistamine with selective peripheral H1-receptor antagonist activity. Both enantiomers of fexofenadine hydrochloride displayed approximately equipotent antihistaminic effects. Fexofenadine inhibited histamine release from peritoneal mast cells in rats. In laboratory animals, no anticholinergic, alpha1-adrenergic or beta-adrenergic-receptor blocking effects were observed. No sedative or other central nervous system effects were observed. Radiolabeled tissue distribution studies in rats indicated that fexofenadine does not cross the blood-brain barrier.
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| 27 |
|
Biaxin XL
18
|
CLARITHROMYCIN |
Abbott Laboratories |
March 2000 |
Disease/s that Drug Treats:Acute Bacterial Exacerbation of Chronic Bronchitis (AECB) and Acute Maxillary Sinusitis
Indications and Usage:
18
BIAXIN Filmtab (clarithromycin tablets, USP) and BIAXIN Granules (clarithromycin for oral suspension, USP) are indicated for the treatment of mild to moderate infections caused by susceptible isolates of the designated bacteria in the conditions as listed below: Adults (BIAXIN Filmtab Tablets and Granules for Oral Suspension) Pharyngitis/Tonsillitis due to Streptococcus pyogenes (The usual drug of choice in the treatment and prevention of streptococcal infections and the prophylaxis of rheumatic fever is penicillin administered by either the intramuscular or the oral route. Clarithromycin is generally effective in the eradication of S. pyogenes from the nasopharynx; however, data establishing the efficacy of clarithromycin in the subsequent prevention of rheumatic fever are not available at present). Acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae. Acute bacterial exacerbation of chronic bronchitis due to Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, or Streptococcus pneumoniae. Community-Acquired Pneumonia due to Haemophilus influenzae, Mycoplasma pneumoniae, Streptococcus pneumoniae, or Chlamydophila pneumoniae (TWAR). Uncomplicated skin and skin structure infections due to Staphylococcus aureus, or Streptococcus pyogenes (Abscesses usually require surgical drainage). Disseminated mycobacterial infections due to Mycobacterium avium, or Mycobacterium intracellulare BIAXIN (clarithromycin) Filmtab tablets in combination with amoxicillin and PREVACID (lansoprazole) or PRILOSEC (omeprazole) Delayed-Release Capsules, as triple therapy, are indicated for the treatment of patients with Helicobacter pylori infection and duodenal ulcer disease (active or five-year history of duodenal ulcer) to eradicate H. pylori. BIAXIN Filmtab tablets in combination with PRILOSEC (omeprazole) capsules or TRITEC (ranitidine bismuth citrate) tablets are also indicated for the treatment of patients with an active duodenal ulcer associated with H. pylori infection. However, regimens which contain clarithromycin as the single antimicrobial agent are more likely to be associated with the development of clarithromycin resistance among patients who fail therapy. Clarithromycincontaining regimens should not be used in patients with known or suspected clarithromycin resistant isolates because the efficacy of treatment is reduced in this setting. In patients who fail therapy, susceptibility testing should be done if possible. If resistance to clarithromycin is demonstrated, a non-clarithromycin-containing therapy is recommended. (For Reference ID: 3836666 information on development of resistance see Microbiology section.) The eradication of H. pylori has been demonstrated to reduce the risk of duodenal ulcer recurrence. Children (BIAXIN Filmtab Tablets and Granules for Oral Suspension) Pharyngitis/Tonsillitis due to Streptococcus pyogenes. Community-Acquired Pneumonia due to Mycoplasma pneumoniae, Streptococcus pneumoniae, or Chlamydophila pneumoniae (TWAR) Acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Acute otitis media due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae NOTE: For information on otitis media, see CLINICAL STUDIES - Otitis Media. Uncomplicated skin and skin structure infections due to Staphylococcus aureus, or Streptococcus pyogenes (Abscesses usually require surgical drainage.) Disseminated mycobacterial infections due to Mycobacterium avium, or Mycobacterium intracellulare Adults (BIAXIN XL Filmtab Tablets) BIAXIN XL Filmtab (clarithromycin extended-release tablets) are indicated for the treatment of adults with mild to moderate infection caused by susceptible strains of the designated microorganisms in the conditions listed below: Acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Acute bacterial exacerbation of chronic bronchitis due to Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Community-Acquired Pneumonia due to Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Chlamydophila pneumoniae (TWAR), or Mycoplasma pneumoniae THE EFFICACY AND SAFETY OF BIAXIN XL IN TREATING OTHER INFECTIONS FOR WHICH OTHER FORMULATIONS OF BIAXIN ARE APPROVED HAVE NOT BEEN ESTABLISHED. Prophylaxis BIAXIN Filmtab tablets and BIAXIN Granules for oral suspension are indicated for the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection. To reduce the development of drug-resistant bacteria and maintain the effectiveness of BIAXIN and other antibacterial drugs, BIAXIN should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying Reference ID: 3836666 antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
DrugBank Targets:
16
50S ribosomal protein L10|Multidrug resistance protein 1|Potassium voltage-gated channel subfamily H member 2|Cytochrome P450 3A4|Solute carrier organic anion transporter family member 1B1|Solute carrier organic anion transporter family member 1B3
Mechanism of Action:
18
Target: -
Action: -
FDA: -
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| 28 |
|
Brovana
18
|
ARFORMOTEROL TARTRATE |
Sepracor |
in October 2006 |
Disease/s that Drug Treats:Chronic Obstructive Pulmonary Disease
Indications and Usage:
18
BROVANA Inhalation Solution is a long-acting beta2-adrenergic agonist (beta2-agonist) indicated for: * Long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. (1.1) Important limitations of use: * BROVANA Inhalation Solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease. (1.2, 5.2) * BROVANA Inhalation Solution is not indicated to treat asthma. (1.2)
DrugBank Targets:
16
Beta-2 adrenergic receptor
Mechanism of Action:
18
Target: beta2-adrenergic
Action: selective bronchodilator
FDA: Arformoterol, the (R,R)-enantiomer of formoterol, is a selective long-acting beta2- adrenergic receptor agonist (beta2-agonist) that has two-fold greater potency than racemic formoterol (which contains both the (S,S) and (R,R)-enantiomers). The (S,S)-enantiomer is about 1,000-fold less potent as a beta2-agonist than the (R,R)-enantiomer. While it is recognized that beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, data indicate that there are also beta2-receptors in the human heart comprising 10% to 50% of the total betaadrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2-agonists may have cardiac effects. The pharmacologic effects of beta2-adrenoceptor agonist drugs, including arformoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'- adenosine monophosphate (cyclic AMP). Increased intracellular cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that arformoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Arformoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-responsiveness. The relevance of these in vitro and animal findings to humans is unknown.
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| 29 |
|
Cedax
18
|
CEFTIBUTEN DIHYDRATE |
Schering-Plough |
December 1995 |
Disease/s that Drug Treats:chronic bronchitis, infection of the middle ear, pharyngitis/tonsillitis
Indications and Usage:
18
CEDAX (ceftibuten) is indicated for the treatment of individuals with mild-to-moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below (see DOSAGE AND ADMINISTRATION and CLINICAL STUDIES sections). Acute Bacterial Exacerbations of Chronic Bronchitis due to Haemophilus influenzae (including β-lactamase-producing strains), Moraxella catarrhalis (including β-lactamaseproducing strains), or Streptococcus pneumoniae (penicillin-susceptible strains only). NOTE: In acute bacterial exacerbations of chronic bronchitis clinical trials where Moraxella catarrhalis was isolated from infected sputum at baseline, ceftibuten clinical efficacy was 22% less than control. Acute Bacterial Otitis Media due to Haemophilus influenzae (including β-lactamase-producing strains), Moraxella catarrhalis (including β-lactamase-producing strains), or Streptococcus pyogenes. NOTE: Although ceftibuten used empirically was equivalent to comparators in the treatment of clinically and/or microbiologically documented acute otitis media, the efficacy against Streptococcus pneumoniae was 23% less than control. Therefore, ceftibuten should be given empirically only when adequate antimicrobial coverage against Streptococcus pneumoniae has been previously administered. Pharyngitis and Tonsillitis due to Streptococcus pyogenes. NOTE: Only penicillin by the intramuscular route of administration has been shown to be effective in the prophylaxis of rheumatic fever. Ceftibuten is generally effective in the eradication of Streptococcus pyogenes from the oropharynx; however, data establishing the efficacy of the CEDAX product for the prophylaxis of subsequent rheumatic fever are not available.
DrugBank Targets:
16
Peptidoglycan synthase FtsI|Penicillin-binding protein 1A|Penicillin-binding protein 1B|Penicillin-binding protein 2
Mechanism of Action:
18
Target: -
Action: -
FDA: -
|
| 30 |
|
Ketek
18
|
TELITHROMYCIN |
Sanofi-aventis |
April 2004 |
Disease/s that Drug Treats:Respiratory Infections
Indications and Usage:
18
KETEK is a ketolide antibacterial indicated for the treatment of community-acquired pneumonia of mild to moderate severity. (1) To reduce the development of drug-resistant bacteria and maintain the effectiveness of KETEK and other antibacterial drugs, KETEK should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. (1)
DrugBank Targets:
16
23S rRNA
Mechanism of Action:
18
Target: domains II and V of 23S rRNA of the 50S ribosomal subunit
Action: blocks protein synthesis
FDA: Telithromycin is a ketolide antibacterial drug. [see Clinical Pharmacology (12.4)] Mechanism of Action Telithromycin belongs to the ketolide class of antibacterials and is structurally related to the macrolides. Telithromycin blocks protein synthesis by binding to domains II and V of 23S rRNA of the 50S ribosomal subunit. Telithromycin may also inhibit the assembly of nascent ribosomal units. Telithromycin concentrates in phagocytes where it exhibits activity against intracellular respiratory pathogens. In vitro, telithromycin has been shown to demonstrate concentrationdependent bactericidal activity against isolates of Streptococcus pneumoniae (including multidrug resistant isolates [MDRSP* ]). *MDRSP=Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are isolates resistant to two or more of the following antimicrobials: penicillin, 2nd generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.
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| 31 |
|
Letairis
18
|
AMBRISENTAN |
Gilead |
June 2007 |
Disease/s that Drug Treats:pulmonary arterial hypertension
Indications and Usage:
18
Letairis is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): * To improve exercise ability and delay clinical worsening. * In combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability. Studies establishing effectiveness included trials predominantly in patients with WHO Functional Class II-III symptoms and etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%) (1).
DrugBank Targets:
16
Endothelin-1 receptor|Endothelin B receptor
Mechanism of Action:
18
Target: endothelin receptor
Action: type-A selective antagonist
FDA: Endothelin-1 (ET-1) is a potent autocrine and paracrine peptide. Two receptor subtypes, ETA and ETB, mediate the effects of ET-1 in the vascular smooth muscle and endothelium. The primary actions of ETA are vasoconstriction and cell proliferation, while the predominant actions of ETB are vasodilation, antiproliferation, and ET-1 clearance. In patients with PAH, plasma ET-1 concentrations are increased as much as 10-fold and correlate with increased mean right atrial pressure and disease severity. ET-1 and ET-1 mRNA concentrations are increased as much as 9-fold in the lung tissue of patients with PAH, primarily in the endothelium of pulmonary arteries. These findings suggest that ET-1 may play a critical role in the pathogenesis and progression of PAH. Ambrisentan is a high-affinity (Ki=0.011 nM) ETA receptor antagonist with a high selectivity for the ETA versus ETB receptor (>4000-fold). The clinical impact of high selectivity for ETA is not known.
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| 32 |
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Patanase
18
|
OLOPATADINE HYDROCHLORIDE |
Alcon |
April 2008 |
Disease/s that Drug Treats:seasonal allergic rhinitis
Indications and Usage:
18
PATANASE Nasal Spray is an H1 receptor antagonist indicated for the relief of the symptoms of seasonal allergic rhinitis in adults and children 6 years of age and older. (1)
DrugBank Targets:
16
Histamine H1 receptor|Protein S100-A1|Protein S100-A12|Protein S100-B|Protein S100-A13|Protein S100-A2
Mechanism of Action:
18
Target: H1 -receptor
Action: selective antagonist
FDA: Olopatadine is a histamine H1 -receptor antagonist. The antihistaminic activity of olopatadine has been documented in isolated tissues, animal models, and humans.
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| 33 |
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Teflaro
18
|
CEFTAROLINE FOSAMIL |
Cerexa |
Nov-10 |
Disease/s that Drug Treats:bacterial skin infections and bacterial pneumonia
Indications and Usage:
18
Teflaro® is a cephalosporin antibacterial indicated for the treatment of the following infections caused by designated susceptible bacteria: * Acute bacterial skin and skin structure infections (ABSSSI) (1.1) * Community-acquired bacterial pneumonia (CABP) (1.2) To reduce the development of drug-resistant bacteria and maintain the effectiveness of Teflaro and other antibacterial drugs, Teflaro should be used only to treat infections that are proven or strongly suspected to be caused by bacteria (1.3).
DrugBank Targets:
-
Mechanism of Action:
18
Target: essential penicillin-binding proteins (PBPs)
Action: -
FDA: Ceftaroline is a cephalosporin antibacterial [see Microbiology (12.4)]. Ceftaroline is a cephalosporin with in vitro activity against Gram-positive and -negative bacteria. The bactericidal action of ceftaroline is mediated through binding to essential penicillin-binding proteins (PBPs). Ceftaroline is bactericidal against S. aureus due to its affinity for PBP2a and against Streptococcus pneumoniae due to its affinity for PBP2x.
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| 34 |
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Tygacil
18
|
TIGECYCLINE |
Wyeth |
2005 |
Disease/s that Drug Treats:complicated skin and skin structure and intra-abdominal infections and bacterial pneumonia
Indications and Usage:
18
TYGACIL is a tetracycline class antibacterial indicated in patients 18 years of age and older for: * Complicated skin and skin structure infections (1.1) * Complicated intra-abdominal infections (1.2) * Community-acquired bacterial pneumonia (1.3) Limitations of Use: TYGACIL is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilatorassociated pneumonia (1.4). To reduce the development of drug-resistant bacteria and maintain the effectiveness of TYGACIL and other antibacterial drugs, TYGACIL should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.
DrugBank Targets:
16
16S rRNA|30S ribosomal protein S9|30S ribosomal protein S12|30S ribosomal protein S13|30S ribosomal protein S14|30S ribosomal protein S19
Mechanism of Action:
18
Target: 30S ribosomal subunit
Action: inhibits protein translation
FDA: Tigecycline is a tetracycline class antibacterial [see Microbiology (12.4)]. Tigecycline inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. In general, tigecycline is considered bacteriostatic; however, TYGACIL has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila.
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