Details of the Drug
General Information of Drug (ID: DM62UG5)
Drug Name |
Vemurafenib
|
|||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Synonyms | PLX4032; RG7204; RO5185426; Zelboraf (TN); Vemurafenib (BRAF inhibitor) | |||||||||||||||||||
Indication |
|
|||||||||||||||||||
Drug Type |
Small molecular drug
|
|||||||||||||||||||
Structure | ||||||||||||||||||||
3D MOL | 2D MOL | |||||||||||||||||||
#Ro5 Violations (Lipinski): 0 | Molecular Weight (mw) | 489.9 | ||||||||||||||||||
Topological Polar Surface Area (xlogp) | 5 | |||||||||||||||||||
Rotatable Bond Count (rotbonds) | 7 | |||||||||||||||||||
Hydrogen Bond Donor Count (hbonddonor) | 2 | |||||||||||||||||||
Hydrogen Bond Acceptor Count (hbondacc) | 7 | |||||||||||||||||||
ADMET Property |
|
|||||||||||||||||||
Chemical Identifiers |
|
|||||||||||||||||||
Cross-matching ID | ||||||||||||||||||||
Molecular Interaction Atlas of This Drug
Drug Therapeutic Target (DTT) |
|
||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Drug Transporter (DTP) |
|
||||||||||||||||||||||||||||||||||||
Drug-Metabolizing Enzyme (DME) |
|
||||||||||||||||||||||||||||||||||||
Molecular Interaction Atlas (MIA) | |||||||||||||||||||||||||||||||||||||
Molecular Expression Atlas of This Drug
The Studied Disease | Melanoma | |||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ICD Disease Classification | 2C30 | |||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||
Molecular Expression Atlas (MEA) | ||||||||||||||||||||||||||||||||||||||||||||||||
Drug-Drug Interaction (DDI) Information of This Drug
Coadministration of a Drug Treating the Same Disease as Vemurafenib
Coadministration of a Drug Treating the Disease Different from Vemurafenib (Comorbidity)
|
Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug
References
1 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5893). | ||||
---|---|---|---|---|---|
2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | ||||
3 | ClinicalTrials.gov (NCT01898585) An Open-Label Study of Zelboraf (Vemurafenib) in Patients With Braf V600 Mutation Positive Metastatic Melanoma. U.S. National Institutes of Health. | ||||
4 | Zhang W, Heinzmann D, Grippo JF: Clinical Pharmacokinetics of Vemurafenib. Clin Pharmacokinet. 2017 Mar 2. doi: 10.1007/s40262-017-0523-7. | ||||
5 | BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs | ||||
6 | A single-dose mass balance and metabolite-profiling study of vemurafenib in patients with metastatic melanoma. Pharmacol Res Perspect. 2015 Mar;3(2):e00113. doi: 10.1002/prp2.113. | ||||
7 | Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66. | ||||
8 | Differential effects of the oncogenic BRAF inhibitor PLX4032 (vemurafenib) and its progenitor PLX4720 on ABCB1 function. J Pharm Pharm Sci. 2014;17(1):154-68. | ||||
9 | Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. | ||||
10 | Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65. | ||||
11 | Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47. | ||||
12 | Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75. | ||||
13 | Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9. | ||||
14 | Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772. | ||||
15 | Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98. | ||||
16 | Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6. | ||||
17 | The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76. | ||||
18 | Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. | ||||
19 | Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007. | ||||
20 | MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8. | ||||
21 | Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64. | ||||
22 | Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31. | ||||
23 | Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. | ||||
24 | Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92. | ||||
25 | Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50. | ||||
26 | Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69. | ||||
27 | Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81. | ||||
28 | Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847. | ||||
29 | The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33. | ||||
30 | Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9. | ||||
31 | Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52. | ||||
32 | FDA Drug Development and Drug Interactions | ||||
33 | LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99. | ||||
34 | Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65. | ||||
35 | Influence of non-steroidal anti-inflammatory drugs on organic anion transporting polypeptide (OATP) 1B1- and OATP1B3-mediated drug transport. Drug Metab Dispos. 2011 Jun;39(6):1047-53. | ||||
36 | Relevance of conserved lysine and arginine residues in transmembrane helices for the transport activity of organic anion transporting polypeptide 1B3. Br J Pharmacol. 2010 Feb 1;159(3):698-708. | ||||
37 | Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705. | ||||
38 | Clinical pipeline report, company report or official report of GlaxoSmithKline (2011). | ||||
39 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | ||||
40 | Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell Melanoma Res. 2014 Mar;27(2):253-62. | ||||
41 | Clinical pipeline report, company report or official report of Ambit Biosciences. | ||||
42 | BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers. Mol Cancer Ther. 2015 Oct;14(10):2187-97. | ||||
43 | National Cancer Institute Drug Dictionary (drug id 688029). | ||||
44 | National Cancer Institute Drug Dictionary (drug id 680347). | ||||
45 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | ||||
46 | Clinical pipeline report, company report or official report of Exelixis (2011). | ||||
47 | Clinical pipeline report, company report or official report of ABM Therapeutics. | ||||
48 | Cerner Multum, Inc. "Australian Product Information.". | ||||
49 | Product Information. Koselugo (selumetinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE. | ||||
50 | Cerner Multum, Inc. "UK Summary of Product Characteristics.". | ||||
51 | Product Information. Zelboraf (vemurafenib). Genentech, South San Francisco, CA. | ||||
52 | Canadian Pharmacists Association. | ||||
53 | Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ. | ||||
54 | Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA. | ||||
55 | Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ. | ||||
56 | Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY. | ||||
57 | Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN. | ||||
58 | Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35. [PMID: 2859674] | ||||
59 | Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ. | ||||
60 | Bruderer S, Aanismaa P, Homery MC, et al. "Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist." AAPS J 14 (2012): 68-78. [PMID: 22189899] | ||||
61 | Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176] | ||||
62 | Product Information. Brintellix (vortioxetine). Takeda Pharmaceuticals America, Lincolnshire, IL. | ||||
63 | Product Information. Aliqopa (copanlisib). Bayer Pharmaceutical Inc, West Haven, CT. | ||||
64 | Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA. | ||||
65 | Product Information. Myrbetriq (mirabegron). Astellas Pharma US, Inc, Deerfield, IL. | ||||
66 | Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ. | ||||
67 | Product Information. Tivicay (dolutegravir). ViiV Healthcare, Research Triangle Park, NC. | ||||
68 | Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC. | ||||
69 | Product Information. Belsomra (suvorexant). Merck & Company Inc, Whitehouse Station, NJ. | ||||
70 | Product Information. Hetlioz (tasimelteon). Vanda Pharmaceuticals Inc, Rockville, MD. | ||||
71 | Product Information. Movantik (naloxegol). Astra-Zeneca Pharmaceuticals, Wilmington, DE. | ||||
72 | Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ. | ||||
73 | Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500] | ||||
74 | Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA. | ||||
75 | Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE. | ||||
76 | Product Information. Imbruvica (ibrutinib). Pharmacyclics Inc, Sunnyvale, CA. | ||||
77 | Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA. | ||||
78 | Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT. | ||||
79 | Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN. | ||||
80 | Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA. | ||||
81 | Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ. | ||||
82 | Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC. | ||||
83 | Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA. | ||||
84 | Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ. | ||||
85 | Product Information. Adempas (riociguat). Bayer Pharmaceutical Inc, West Haven, CT. | ||||
86 | Product Information. Odomzo (sonidegib). Novartis Pharmaceuticals, East Hanover, NJ. | ||||
87 | Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY. | ||||
88 | Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA. | ||||
89 | EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.". | ||||
90 | Product Information. Tradjenta (linagliptin). Boehringer Ingelheim, Ridgefield, CT. | ||||
91 | Product Information. Orilissa (elagolix). AbbVie US LLC, North Chicago, IL. | ||||