Identification

Name
Vemurafenib
Accession Number
DB08881  (DB05238)
Type
Small Molecule
Groups
Approved
Description

Vemurafenib is a competitive kinase inhibitor with activity against BRAF kinase with mutations like V600E.[2] It exerts its function by binding to the ATP-binding domain of the mutant BRAF.[3] Vemurafenib was co-developed by Roche and Plexxikon and it obtained its FDA approval on August 17, 2011, under the company Hoffmann La Roche. After approval, Roche in collaboration with Genentech launched a broad development program. [8]

Structure
Thumb
Synonyms
  • BRAF(V600E) Kinase Inhibitor RO5185426
External IDs
PLX-4032 / PLX4032 / RG-7204 / RG7204 / RO-51-85426 / RO-5185426 / RO5185426
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ZelborafTablet240 mgOralHoffmann La Roche2012-03-05Not applicableCanada
ZelborafTablet, film coated240 mgOralRoche Registration Limited2012-02-17Not applicableEu
ZelborafTablet, film coated240 mg/1OralGenentech, Inc.2011-08-17Not applicableUs
Categories
UNII
207SMY3FQT
CAS number
918504-65-1
Weight
Average: 489.922
Monoisotopic: 489.072546264
Chemical Formula
C23H18ClF2N3O3S
InChI Key
GPXBXXGIAQBQNI-UHFFFAOYSA-N
InChI
InChI=1S/C23H18ClF2N3O3S/c1-2-9-33(31,32)29-19-8-7-18(25)20(21(19)26)22(30)17-12-28-23-16(17)10-14(11-27-23)13-3-5-15(24)6-4-13/h3-8,10-12,29H,2,9H2,1H3,(H,27,28)
IUPAC Name
N-{3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide
SMILES
CCCS(=O)(=O)NC1=C(F)C(C(=O)C2=CNC3=NC=C(C=C23)C2=CC=C(Cl)C=C2)=C(F)C=C1

Pharmacology

Indication

Vemurafenib is approved since 2011 for the treatment of metastatic melanoma with a mutation on BRAF in the valine located in the exon 15 at codon 600, this mutation is denominated as V600E.[3] The V600E mutation, a substitution of glutamic acid for valine, accounts for 54% of the cases of cutaneous melanoma.[4] Vemurafenib approval was extended in 2017, for its use as a treatment of adult patients with Erdheim-Chester Disease whose cancer cells present BRAF V600 mutation.[9] Erdheim-Chester disease is an extremely rare histiocyte cell disorder that affects large bones, large vessels, central nervous system, as well as, skin and lungs. It is reported an association of Erdheim-Chester disease and V600E mutation.[5]

Structured Indications
Pharmacodynamics

BRAF activation results in cell growth, proliferation, and metastasis. BRAF is an intermediary molecule in MAPK whose activation depends on ERK activation, elevation of cyclin D1 and cellular proliferation. The mutation V600E produces a constitutively form of BRAF. Vemurafenib has been shown to reduce all activation markers related to BRAF; in clinical trials, vemurafenib treatment showed a reduction of cytoplasmic phosphorylated ERK and a cell proliferation driven by Ki-67. Studies also reported decrease in MAPK-related metabolic activity.[3] All the different reports indicate thet Vemurafenib generates an almost complete inhibition of the MAPK pathway.

Mechanism of action

Vemurafenib is an orally available inhibitor of mutated BRAF-serine-threonine kinase. Vemurafenif is a small molecule that interacts as a competitive inhibitor of the mutated species of BRAF. It is especially potent against the BRAF V600E mutation. Vemurafenib blocks downstream processes to inhibit tumour growth and eventually trigger apoptosis. Vemurafenib does not have antitumour effects against melanoma cell lines with the wild-type BRAF mutation.[10]

TargetActionsOrganism
ASerine/threonine-protein kinase B-raf
inhibitor
Human
Absorption

Vemurafenib is well absorbed after oral administration.[6] Peak concentrations are reached in 3 hours when an oral dose of 960 mg twice daily for 15 days has been given to patients. In the same conditions, Vemurafenib presents a Cmax of 62 mcg/ml and AUC of 601 mcg h/ml.[FDA Label] It is unknown how food affects the absorption of vemurafenib. It presents an accumulation ratio of 7.36 after repeating doses of 960 mg [10]

Volume of distribution

The estimation of the volume of distribution for Vemurafenib is 106 L.[7]

Protein binding

Vemurafenib highly binds to plasma proteins where >99% of the administered dose will be found protein bound to serum albumin and alpha-1 acid glycoprotein.[7]

Metabolism

Vemurafenib is metabolized by CYP3A4 and the metabolites make up 5% of the components in plasma. The parent compound makes up for the remaining 95%.[7]

Route of elimination

Analysis showed that 94% of administered Vemurafenib is excreted via feces and 1% is excreted by urine.[7]

Half life

The elimination half-life of Vemurafenib is estimated to be 57 hours (range of 30-120 hours).[7]

Clearance

The total body clearance is 31 L/day.[7]

Toxicity

In the few toxicity reports, it has been shown an increased in the development of cutaneous squamous cell carcinomas or acceleration in pre-existant tumor growth.[FDA Label]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Vemurafenib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Vemurafenib.Experimental
AlfuzosinAlfuzosin may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
AmantadineAmantadine may increase the QTc-prolonging activities of Vemurafenib.Approved
AmoxapineAmoxapine may increase the QTc-prolonging activities of Vemurafenib.Approved
ApomorphineApomorphine may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
ArformoterolArformoterol may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Vemurafenib.Approved, Investigational
Arsenic trioxideThe risk or severity of QTc prolongation can be increased when Arsenic trioxide is combined with Vemurafenib.Approved, Investigational
ArtemetherThe risk or severity of QTc prolongation can be increased when Artemether is combined with Vemurafenib.Approved
AtomoxetineAtomoxetine may increase the QTc-prolonging activities of Vemurafenib.Approved
AzithromycinAzithromycin may increase the QTc-prolonging activities of Vemurafenib.Approved
BedaquilineBedaquiline may increase the QTc-prolonging activities of Vemurafenib.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Vemurafenib.Approved, Investigational
BosentanThe serum concentration of Vemurafenib can be decreased when it is combined with Bosentan.Approved, Investigational
BuserelinBuserelin may increase the QTc-prolonging activities of Vemurafenib.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Vemurafenib.Approved
CeritinibThe serum concentration of Vemurafenib can be increased when it is combined with Ceritinib.Approved
ChloroquineChloroquine may increase the QTc-prolonging activities of Vemurafenib.Approved, Vet Approved
CiprofloxacinCiprofloxacin may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
CitalopramThe risk or severity of QTc prolongation can be increased when Citalopram is combined with Vemurafenib.Approved
ClemastineThe metabolism of Vemurafenib can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Vemurafenib can be decreased when combined with Clotrimazole.Approved, Vet Approved
ConivaptanThe serum concentration of Vemurafenib can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Vemurafenib can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Vemurafenib.Approved, Investigational
CyclosporineThe metabolism of Vemurafenib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Vemurafenib.Experimental
DabrafenibThe serum concentration of Vemurafenib can be decreased when it is combined with Dabrafenib.Approved
DeferasiroxThe serum concentration of Vemurafenib can be decreased when it is combined with Deferasirox.Approved, Investigational
DegarelixDegarelix may increase the QTc-prolonging activities of Vemurafenib.Approved
DelavirdineThe metabolism of Vemurafenib can be decreased when combined with Delavirdine.Approved
DesfluraneDesflurane may increase the QTc-prolonging activities of Vemurafenib.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Vemurafenib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Vemurafenib.Approved, Investigational
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Vemurafenib.Approved
DihydroergotamineThe metabolism of Vemurafenib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Vemurafenib can be decreased when combined with Diltiazem.Approved
DisopyramideThe risk or severity of QTc prolongation can be increased when Disopyramide is combined with Vemurafenib.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Vemurafenib.Approved, Investigational
DofetilideThe risk or severity of QTc prolongation can be increased when Dofetilide is combined with Vemurafenib.Approved
DolasetronDolasetron may increase the QTc-prolonging activities of Vemurafenib.Approved
DoxycyclineThe metabolism of Vemurafenib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Vemurafenib can be decreased when combined with Dronedarone.Approved
DroperidolDroperidol may increase the QTc-prolonging activities of Vemurafenib.Approved, Vet Approved
EliglustatThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Vemurafenib can be decreased when it is combined with Enzalutamide.Approved
EribulinEribulin may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
ErythromycinThe metabolism of Vemurafenib can be decreased when combined with Erythromycin.Approved, Vet Approved
EscitalopramThe risk or severity of QTc prolongation can be increased when Escitalopram is combined with Vemurafenib.Approved, Investigational
EzogabineEzogabine may increase the QTc-prolonging activities of Vemurafenib.Approved
FamotidineFamotidine may increase the QTc-prolonging activities of Vemurafenib.Approved
FelbamateFelbamate may increase the QTc-prolonging activities of Vemurafenib.Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Vemurafenib.Approved
FingolimodFingolimod may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
FlecainideFlecainide may increase the QTc-prolonging activities of Vemurafenib.Approved, Withdrawn
FluconazoleFluconazole may increase the QTc-prolonging activities of Vemurafenib.Approved
FlupentixolThe risk or severity of QTc prolongation can be increased when Flupentixol is combined with Vemurafenib.Approved, Withdrawn
FormoterolFormoterol may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
FosamprenavirThe metabolism of Vemurafenib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Vemurafenib can be increased when it is combined with Fosaprepitant.Approved
FoscarnetFoscarnet may increase the QTc-prolonging activities of Vemurafenib.Approved
Fusidic AcidThe serum concentration of Vemurafenib can be increased when it is combined with Fusidic Acid.Approved
Gadobenic acidGadobenic acid may increase the QTc-prolonging activities of Vemurafenib.Approved
GalantamineGalantamine may increase the QTc-prolonging activities of Vemurafenib.Approved
GemifloxacinGemifloxacin may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Vemurafenib.Experimental
GoserelinGoserelin may increase the QTc-prolonging activities of Vemurafenib.Approved
GranisetronGranisetron may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
HistrelinHistrelin may increase the QTc-prolonging activities of Vemurafenib.Approved
HydroxyzineHydroxyzine may increase the QTc-prolonging activities of Vemurafenib.Approved
IbandronateIbandronate may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
IbutilideThe risk or severity of QTc prolongation can be increased when Ibutilide is combined with Vemurafenib.Approved
IdelalisibThe serum concentration of Vemurafenib can be increased when it is combined with Idelalisib.Approved
IndacaterolIndacaterol may increase the QTc-prolonging activities of Vemurafenib.Approved
IndapamideIndapamide may increase the QTc-prolonging activities of Vemurafenib.Approved
IsavuconazoniumThe metabolism of Vemurafenib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsofluraneIsoflurane may increase the QTc-prolonging activities of Vemurafenib.Approved, Vet Approved
IsradipineIsradipine may increase the QTc-prolonging activities of Vemurafenib.Approved
IvabradineIvabradine may increase the QTc-prolonging activities of Vemurafenib.Approved
IvacaftorThe serum concentration of Vemurafenib can be increased when it is combined with Ivacaftor.Approved
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Vemurafenib.Experimental
LapatinibLapatinib may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
LenvatinibLenvatinib may increase the QTc-prolonging activities of Vemurafenib.Approved
LeuprolideLeuprolide may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
LevofloxacinLevofloxacin may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
LithiumLithium may increase the QTc-prolonging activities of Vemurafenib.Approved
LovastatinThe metabolism of Vemurafenib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Vemurafenib can be increased when it is combined with Luliconazole.Approved
LumefantrineThe risk or severity of QTc prolongation can be increased when Lumefantrine is combined with Vemurafenib.Approved
MefloquineMefloquine may increase the QTc-prolonging activities of Vemurafenib.Approved
MethotrimeprazineMethotrimeprazine may increase the QTc-prolonging activities of Vemurafenib.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Vemurafenib.Experimental
MetoclopramideMetoclopramide may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Vemurafenib.Approved, Investigational
MetronidazoleMetronidazole may increase the QTc-prolonging activities of Vemurafenib.Approved
MifepristoneThe serum concentration of Vemurafenib can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronMirabegron may increase the QTc-prolonging activities of Vemurafenib.Approved
MitotaneThe serum concentration of Vemurafenib can be decreased when it is combined with Mitotane.Approved
MoexiprilMoexipril may increase the QTc-prolonging activities of Vemurafenib.Approved
MoxifloxacinMoxifloxacin may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
NetupitantThe serum concentration of Vemurafenib can be increased when it is combined with Netupitant.Approved
NicardipineNicardipine may increase the QTc-prolonging activities of Vemurafenib.Approved
NilotinibThe metabolism of Vemurafenib can be decreased when combined with Nilotinib.Approved, Investigational
NorfloxacinNorfloxacin may increase the QTc-prolonging activities of Vemurafenib.Approved
OctreotideOctreotide may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
OfloxacinOfloxacin may increase the QTc-prolonging activities of Vemurafenib.Approved
OlaparibThe metabolism of Vemurafenib can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Vemurafenib.Experimental, Investigational
OlodaterolOlodaterol may increase the QTc-prolonging activities of Vemurafenib.Approved
OsimertinibThe serum concentration of Vemurafenib can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Vemurafenib.Approved
OxytocinOxytocin may increase the QTc-prolonging activities of Vemurafenib.Approved, Vet Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Vemurafenib.Approved, Vet Approved
PalbociclibThe serum concentration of Vemurafenib can be increased when it is combined with Palbociclib.Approved
PaliperidoneThe risk or severity of QTc prolongation can be increased when Paliperidone is combined with Vemurafenib.Approved
PanobinostatPanobinostat may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
ParoxetineParoxetine may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
PasireotidePasireotide may increase the QTc-prolonging activities of Vemurafenib.Approved
PerflutrenPerflutren may increase the QTc-prolonging activities of Vemurafenib.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Vemurafenib.Experimental
ProcainamideThe risk or severity of QTc prolongation can be increased when Procainamide is combined with Vemurafenib.Approved
PromethazinePromethazine may increase the QTc-prolonging activities of Vemurafenib.Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Vemurafenib.Experimental
ProtriptylineProtriptyline may increase the QTc-prolonging activities of Vemurafenib.Approved
QuetiapineThe risk or severity of QTc prolongation can be increased when Quetiapine is combined with Vemurafenib.Approved
QuinidineThe risk or severity of QTc prolongation can be increased when Quinidine is combined with Vemurafenib.Approved
RanolazineRanolazine may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
RilpivirineRilpivirine may increase the QTc-prolonging activities of Vemurafenib.Approved
RisperidoneRisperidone may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
RolapitantThe serum concentration of Vemurafenib can be increased when it is combined with Rolapitant.Approved
SalbutamolSalbutamol may increase the QTc-prolonging activities of Vemurafenib.Approved, Vet Approved
SalmeterolSalmeterol may increase the QTc-prolonging activities of Vemurafenib.Approved
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Vemurafenib.Approved
SevofluraneSevoflurane may increase the QTc-prolonging activities of Vemurafenib.Approved, Vet Approved
SildenafilThe metabolism of Vemurafenib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Vemurafenib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Vemurafenib can be increased when it is combined with Simeprevir.Approved
SolifenacinSolifenacin may increase the QTc-prolonging activities of Vemurafenib.Approved
SorafenibSorafenib may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
SotalolThe risk or severity of QTc prolongation can be increased when Sotalol is combined with Vemurafenib.Approved
St. John's WortThe serum concentration of Vemurafenib can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Vemurafenib can be increased when it is combined with Stiripentol.Approved
SulfamethoxazoleSulfamethoxazole may increase the QTc-prolonging activities of Vemurafenib.Approved
SulfisoxazoleThe metabolism of Vemurafenib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SunitinibSunitinib may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
TelavancinTelavancin may increase the QTc-prolonging activities of Vemurafenib.Approved
TerbutalineTerbutaline may increase the QTc-prolonging activities of Vemurafenib.Approved
TeriflunomideThe serum concentration of Vemurafenib can be increased when it is combined with Teriflunomide.Approved
TetrabenazineThe risk or severity of QTc prolongation can be increased when Tetrabenazine is combined with Vemurafenib.Approved
TiclopidineThe metabolism of Vemurafenib can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Vemurafenib can be decreased when it is combined with Tocilizumab.Approved
TolterodineTolterodine may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Vemurafenib.Approved, Investigational
TrazodoneTrazodone may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
TreprostinilTreprostinil may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
TrimethoprimTrimethoprim may increase the QTc-prolonging activities of Vemurafenib.Approved, Vet Approved
TrimipramineTrimipramine may increase the QTc-prolonging activities of Vemurafenib.Approved
TriptorelinTriptorelin may increase the QTc-prolonging activities of Vemurafenib.Approved, Vet Approved
VandetanibThe risk or severity of QTc prolongation can be increased when Vandetanib is combined with Vemurafenib.Approved
VardenafilVardenafil may increase the QTc-prolonging activities of Vemurafenib.Approved
VenlafaxineVenlafaxine may increase the QTc-prolonging activities of Vemurafenib.Approved
VilanterolVilanterol may increase the QTc-prolonging activities of Vemurafenib.Approved
VorinostatVorinostat may increase the QTc-prolonging activities of Vemurafenib.Approved, Investigational
ZuclopenthixolThe risk or severity of QTc prolongation can be increased when Zuclopenthixol is combined with Vemurafenib.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]
  2. Kim G, McKee AE, Ning YM, Hazarika M, Theoret M, Johnson JR, Xu QC, Tang S, Sridhara R, Jiang X, He K, Roscoe D, McGuinn WD, Helms WS, Russell AM, Miksinski SP, Zirkelbach JF, Earp J, Liu Q, Ibrahim A, Justice R, Pazdur R: FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation. Clin Cancer Res. 2014 Oct 1;20(19):4994-5000. doi: 10.1158/1078-0432.CCR-14-0776. Epub 2014 Aug 5. [PubMed:25096067]
  3. Luke JJ, Hodi FS: Vemurafenib and BRAF inhibition: a new class of treatment for metastatic melanoma. Clin Cancer Res. 2012 Jan 1;18(1):9-14. doi: 10.1158/1078-0432.CCR-11-2197. Epub 2011 Nov 14. [PubMed:22083257]
  4. Schirosi L, Strippoli S, Gaudio F, Graziano G, Popescu O, Guida M, Simone G, Mangia A: Is immunohistochemistry of BRAF V600E useful as a screening tool and during progression disease of melanoma patients? BMC Cancer. 2016 Nov 18;16(1):905. [PubMed:27863476]
  5. Stempel JM, Bustamante Alvarez JG, Carpio AM, Mittal V, Dourado C: Erdheim-Chester disease, moving away from the orphan diseases: A case report. Respir Med Case Rep. 2016 Dec 3;20:55-58. eCollection 2017. [PubMed:27995058]
  6. Zhang W, Heinzmann D, Grippo JF: Clinical Pharmacokinetics of Vemurafenib. Clin Pharmacokinet. 2017 Mar 2. doi: 10.1007/s40262-017-0523-7. [PubMed:28255850]
  7. Goldinger SM, Rinderknecht J, Dummer R, Kuhn FP, Yang KH, Lee L, Ayala RC, Racha J, Geng W, Moore D, Liu M, Joe AK, Bazan SP, Grippo JF: 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. [PubMed:25729580]
  8. Roche news [Link]
  9. FDA News and Events [Link]
  10. FDA Vemurafenib application [Link]
External Links
KEGG Drug
D09996
PubChem Compound
42611257
PubChem Substance
175427131
ChemSpider
24747352
BindingDB
50396483
ChEBI
63637
ChEMBL
CHEMBL1229517
PharmGKB
PA165946873
HET
032
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vemurafenib
ATC Codes
L01XE15 — Vemurafenib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
3og7 / 4rzv / 5hes
FDA label
Download (304 KB)
MSDS
Download (51 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentPediatric Recurrent/Refractory BRAFV600E-mutant Gliomas1
1Active Not RecruitingTreatmentAdvanced Cancers1
1Active Not RecruitingTreatmentCancer, Advanced / Tumors, Solid1
1Active Not RecruitingTreatmentCarcinoma, Colorectal / Malignant Melanoma1
1Active Not RecruitingTreatmentMalignant Melanoma3
1Active Not RecruitingTreatmentMelanoma3
1Active Not RecruitingTreatmentNeoplasms1
1CompletedNot AvailableMalignant Melanoma, Neoplasms2
1CompletedBasic ScienceMalignant Melanoma, Cancer1
1CompletedOtherMalignant Melanoma, Neoplasms1
1CompletedTreatmentMalignant Melanoma4
1CompletedTreatmentMalignant Melanoma, Neoplasms2
1CompletedTreatmentMetastatic Colorectal Cancers1
1CompletedTreatmentNeoplasms Malignant1
1CompletedTreatmentThyroid Cancers1
1RecruitingTreatmentAdvanced Cancers2
1RecruitingTreatmentMelanoma1
1RecruitingTreatmentMelanoma / Skin Cancers1
1RecruitingTreatmentMetastatic Melanoma, BRAF V600 Mutation Positive1
1SuspendedTreatmentAdvanced or Inoperable Malignant Melanoma With BRAF Mutation1
1TerminatedTreatmentMalignant Melanoma1
1TerminatedTreatmentMelanoma2
1TerminatedTreatmentMelanoma / Metastatic Cancers1
1TerminatedTreatmentRecurrent Melanoma / Stage IIIA Melanoma / Stage IIIB Melanoma / Stage IIIc Melanoma / Stage IV Melanoma / Unspecified Adult Solid Tumor, Protocol Specific1
1TerminatedTreatmentStage III or Stage IV Metastatic Melanoma That Has Not Been Previously Treated With a Selective BRAF Inhibitor / V600-mutated BRAF Metastatic Melanoma / V600-mutated BRAF Unresectable Melanoma1
1WithdrawnTreatmentBRAFV600 Mutation / Stage IV Melanoma1
1WithdrawnTreatmentMalignant Melanoma, Neoplasms1
1WithdrawnTreatmentMelanoma1
1WithdrawnTreatmentNeoplasms1
1WithdrawnTreatmentRecurrent Melanoma / Stage IV Melanoma / Tumors Metastatic to Brain1
1, 2Active Not RecruitingTreatmentMelanoma1
1, 2Not Yet RecruitingTreatmentMelanoma1
1, 2RecruitingTreatmentBRAF-mutated Metastatic Melanoma / Melanoma / Metastatic Melanoma / V600EBRAF-mutated Metastatic Melanoma1
1, 2RecruitingTreatmentMalignant Lymphomas / Tumors, Solid1
1, 2RecruitingTreatmentMelanoma2
1, 2RecruitingTreatmentMetastatic Melanoma1
1, 2TerminatedTreatmentAdvanced BRAF-mutant Cancers1
1, 2Unknown StatusTreatmentBRAF Mutant Metastatic Melanoma1
1, 2WithdrawnTreatmentMultiple Myeloma (MM)1
2Active Not RecruitingTreatmentColorectal Cancers1
2Active Not RecruitingTreatmentHairy Cell Leukemia (HCL)1
2Active Not RecruitingTreatmentMelanoma1
2Active Not RecruitingTreatmentMetastatic Cancers1
2Active Not RecruitingTreatmentMetastatic Melanoma1
2Active Not RecruitingTreatmentMultiple Myeloma, Neoplasms1
2CompletedTreatmentMalignant Melanoma3
2CompletedTreatmentMalignant Melanoma Stage IV1
2CompletedTreatmentMelanoma1
2CompletedTreatmentMelanoma [C04.557.465.625.650.510]1
2CompletedTreatmentNeoplasms1
2Not Yet RecruitingTreatmentBRAF V600E Mutation Present / Papillary Craniopharyngioma1
2Not Yet RecruitingTreatmentMelanoma, Malignant, of Soft Parts1
2Not Yet RecruitingTreatmentMelanoma / Melanoma (Skin) / Melanoma Stage1
2RecruitingScreeningMetastatic Melanoma / Metastatic Melanoma, BRAF V600 Mutation Positive1
2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / BRAF NP_004324.2:p.V600X / Ependymomas / Ewing's Sarcoma (ES) / Hepatoblastomas / Histiocytosis / Langerhans Cell Histiocytosis (LCH) / Malignant Germ Cell Tumor / Malignant Gliomas / Peripheral Primitive Neuroectodermal Tumor / Recurrent Childhood Central Nervous System Neoplasm / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Malignant Solid Neoplasm / Recurrent Neuroblastoma / Refractory Central Nervous System Neoplasm / Refractory Malignant Solid Neoplasm / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Rhabdoid Tumors / Rhabdomyosarcomas / Sarcoma, Osteogenic / Soft Tissue Sarcoma (STS) / Stage III Childhood Non-Hodgkin Lymphoma / Stage IV Childhood Non-Hodgkin Lymphoma / Wilms' tumor1
2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Childhood Langerhans Cell Histiocytosis / Histiocytic Sarcoma (HS) / Juvenile Xanthogranuloma / Langerhans Cell Histiocytosis (LCH) / Malignant Gliomas / Malignant Lymphomas / Recurrent Central Nervous System Neoplasm / Recurrent Childhood Ependymoma / Recurrent Childhood Malignant Germ Cell Tumor / Recurrent Childhood Medulloblastoma / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Childhood Soft Tissue Sarcoma / Recurrent Ewing Sarcoma / Recurrent Gliomas / Recurrent Hepatoblastoma / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Solid Neoplasm / Recurrent Neuroblastoma / Recurrent Osteosarcoma / Recurrent Peripheral Primitive Neuroectodermal Tumor / Refractory Central Nervous System Neoplasm / Refractory Childhood Malignant Germ Cell Tumor / Refractory Langerhans cell histiocytosis / Refractory Malignant Solid Neoplasm / Refractory Neuroblastoma / Rhabdoid Tumors / Stage III Childhood Non-Hodgkin Lymphoma / Stage III Osteosarcoma / Stage III Osteosarcoma AJCC v7 / Stage III Soft Tissue Sarcoma / Stage III Soft Tissue Sarcoma AJCC v7 / Stage IV Childhood Non-Hodgkin Lymphoma / Stage IV Osteosarcoma / Stage IV Osteosarcoma AJCC v7 / Stage IV Soft Tissue Sarcoma / Stage IV Soft Tissue Sarcoma AJCC v7 / Stage IVA Osteosarcoma / Stage IVA Osteosarcoma AJCC v7 / Stage IVB Osteosarcoma / Stage IVB Osteosarcoma AJCC v7 / Wilms' tumor1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentAnaplastic Thyroid Carcinoma / Malignant Neoplasms of Thyroid and Other Endocrine Glands / Poorly Differentiated Thyroid Cancer1
2RecruitingTreatmentCancers / Neoplasia / Neoplasms / Tumors1
2RecruitingTreatmentColorectal Cancers1
2RecruitingTreatmentHematologic Cancers / Metastatic Cancers / Tumors, Solid1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentMalignant Melanoma2
2RecruitingTreatmentMelanoma2
2RecruitingTreatmentNeoplasms1
2RecruitingTreatmentRare Tumor / Refractory Tumors1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2RecruitingTreatmentStage IIIB-C Melanoma1
2RecruitingTreatmentThyroid Cancers1
2TerminatedTreatmentActive Melanoma Brain Metastases1
2TerminatedTreatmentMalignant Melanoma2
2TerminatedTreatmentMelanoma3
2TerminatedTreatmentMelanoma / Metastatic Melanoma1
2TerminatedTreatmentMetastatic Melanoma (Carrying BRAF V600 Mutation)1
2Unknown StatusTreatmentMalignant Melanoma1
3Active Not RecruitingTreatmentMalignant Melanoma1
3Active Not RecruitingTreatmentMalignant Melanoma / Melanoma1
3Active Not RecruitingTreatmentMelanoma2
3CompletedTreatmentMalignant Melanoma2
3RecruitingTreatmentMelanoma1
3WithdrawnTreatmentMelanoma1
4Active Not RecruitingTreatmentMalignant Melanoma1
4RecruitingTreatmentNeoplasms1
Not AvailableActive Not RecruitingNot AvailableMelanoma1
Not AvailableActive Not RecruitingDiagnosticAdvanced Solid Tumors / Cancers1
Not AvailableActive Not RecruitingTreatmentThyroid Carcinoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral240 mg
Tablet, film coatedOral240 mg
Tablet, film coatedOral240 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8470818No2006-08-022026-08-02Us
US8143271No2006-06-212026-06-21Us
US7863288No2009-06-202029-06-20Us
US7504509No2006-10-222026-10-22Us
US8741920No2010-07-272030-07-27Us
US9447089No2012-06-062032-06-06Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)272°CMSDS
water solubility<1 mg/mL MSDS
logP5.1MSDS
Caco2 permeability2.9E-06FDA review
pKa7.1Royal Soc Chem
Predicted Properties
PropertyValueSource
Water Solubility0.000362 mg/mLALOGPS
logP4.95ALOGPS
logP4.62ChemAxon
logS-6.1ALOGPS
pKa (Strongest Acidic)7.17ChemAxon
pKa (Strongest Basic)3.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area91.92 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity121.97 m3·mol-1ChemAxon
Polarizability48.1 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.745
Caco-2 permeable-0.6222
P-glycoprotein substrateNon-substrate0.6215
P-glycoprotein inhibitor INon-inhibitor0.5884
P-glycoprotein inhibitor IINon-inhibitor0.699
Renal organic cation transporterNon-inhibitor0.864
CYP450 2C9 substrateNon-substrate0.7628
CYP450 2D6 substrateNon-substrate0.8038
CYP450 3A4 substrateSubstrate0.5645
CYP450 1A2 substrateInhibitor0.5762
CYP450 2C9 inhibitorInhibitor0.5987
CYP450 2D6 inhibitorNon-inhibitor0.7329
CYP450 2C19 inhibitorInhibitor0.6508
CYP450 3A4 inhibitorInhibitor0.7061
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9553
Ames testNon AMES toxic0.6323
CarcinogenicityNon-carcinogens0.7229
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5179 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6688
hERG inhibition (predictor II)Non-inhibitor0.5302
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-0024900000-4911e6c7ad52fd2c2896

Taxonomy

Description
This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
Phenylpyridines / Sulfanilides / Pyrrolopyridines / Benzoyl derivatives / Chlorobenzenes / Fluorobenzenes / Organosulfonamides / Organic sulfonamides / Aryl chlorides / Aryl fluorides
show 12 more
Substituents
Aryl-phenylketone / 3-phenylpyridine / Sulfanilide / Pyrrolopyridine / Benzoyl / Halobenzene / Fluorobenzene / Chlorobenzene / Aryl chloride / Aryl halide
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, sulfonamide, organochlorine compound, pyrrolopyridine (CHEBI:63637)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, a...
Gene Name
BRAF
Uniprot ID
P15056
Uniprot Name
Serine/threonine-protein kinase B-raf
Molecular Weight
84436.135 Da
References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Mittapalli RK, Vaidhyanathan S, Sane R, Elmquist WF: Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032). J Pharmacol Exp Ther. 2012 Jul;342(1):33-40. doi: 10.1124/jpet.112.192195. Epub 2012 Mar 27. [PubMed:22454535]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Mittapalli RK, Vaidhyanathan S, Sane R, Elmquist WF: Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032). J Pharmacol Exp Ther. 2012 Jul;342(1):33-40. doi: 10.1124/jpet.112.192195. Epub 2012 Mar 27. [PubMed:22454535]

Drug created on May 20, 2013 00:41 / Updated on November 22, 2017 12:37