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Details

Stereochemistry ACHIRAL
Molecular Formula C23H18ClF2N3O3S
Molecular Weight 489.922
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VEMURAFENIB

SMILES

CCCS(=O)(=O)NC1=C(F)C(C(=O)C2=CNC3=C2C=C(C=N3)C4=CC=C(Cl)C=C4)=C(F)C=C1

InChI

InChIKey=GPXBXXGIAQBQNI-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C23H18ClF2N3O3S
Molecular Weight 489.922
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Vemurafenib (trade name Zelboraf) is a low molecular weight, orally available kinase inhibitor. It inhibits of some mutated forms of BRAF serinethreonine kinase, including BRAF V600E and is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5 and FGR at similar concentrations. Vemurafenib is not recommended for use in patients with wild-type BRAF melanoma. Zelboraf does not cure melanoma, but stops it's progression. Some 26% of patients in clinical trials developed a non melanoma form of skin cancer called cutaneous squamous cell carcinoma, which can usually be removed via relatively simple surgery. Other side effects include joint pain, rash, hair loss, fatigue, nausea, and skin sensitivity to sunlight. Patients taking Zelboraf must avoid sun exposure. It's not yet clear how long Zelboraf can increase melanoma survival.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
31.0 nM [IC50]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas.
2010 Dec
Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma.
2010 Sep 30
The BRAFT1799A mutation confers sensitivity of thyroid cancer cells to the BRAFV600E inhibitor PLX4032 (RG7204).
2011 Jan 28
Novel immunotherapeutic agents and small molecule antagonists of signalling kinases for the treatment of metastatic melanoma.
2011 Jul 9
Improved survival with vemurafenib in melanoma with BRAF V600E mutation.
2011 Jun 30
Overcoming metastatic melanoma with BRAF inhibitors.
2011 May
BRAF targeted therapy changes the treatment paradigm in melanoma.
2011 May 24
New drugs in melanoma: it's a whole new world.
2011 Sep
Vemurafenib for the treatment of melanoma.
2012 Dec
Conformation-specific effects of Raf kinase inhibitors.
2012 Sep 13
A multisite blinded study for the detection of BRAF mutations in formalin-fixed, paraffin-embedded malignant melanoma.
2013
BRAF inhibitor activity in V600R metastatic melanoma.
2013 Mar
Characterization of vemurafenib phototoxicity in a mouse model.
2014 Jan
Identification of recurrent SMO and BRAF mutations in ameloblastomas.
2014 Jul
Copper is required for oncogenic BRAF signalling and tumorigenesis.
2014 May 22
Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells.
2015 Aug 18
The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells.
2015 Jan 16
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers.
2015 Sep 14
Patents

Sample Use Guides

In Vivo Use Guide
960 mg twice daily. Administer ZELBORAF approximately 12 hours apart with or without a meal. Management of symptomatic adverse drug reactions may require dose reduction, treatment interruption, or treatment discontinuation of ZELBORAF. Dose reductions resulting in a dose below 480 mg twice daily are not recommended
Route of Administration: Oral
In Vitro Use Guide
The antitumor effects of vemurafenib against SM1 cells were tested by in vitro MTS cell proliferation assay after 72 hours of treatment. The IC50 of vemurafenib was 14 uM, which is approximately one log higher than the sensitivity of M229 (IC50 of 0.5 uM), a BRAF V600E mutant human melanoma cell line highly sensitive to vemurafenib, and at a similar range as the relatively resistant BRAF V600E mutant human melanoma cell line M233 (IC50 of 15 uM).
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:54:17 UTC 2019
Edited
by admin
on Mon Oct 21 20:54:17 UTC 2019
Record UNII
207SMY3FQT
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VEMURAFENIB
DASH   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
RG 7204
Code English
VEMURAFENIB [ORANGE BOOK]
Common Name English
ZELBORAF
Brand Name English
N-(3-((5-(4-CHLOROPHENYL)-1H-PYRROLO(2,3-B)PYRIDIN-3-YL)CARBONYL)-2,4- DIFLUOROPHENYL)PROPANE-1-SULFONAMIDE
Systematic Name English
VEMURAFENIB [VANDF]
Common Name English
RO-51-85426
Code English
VEMURAFENIB [MART.]
Common Name English
VEMURAFENIB [USAN]
Common Name English
VEMURAFENIB [WHO-DD]
Common Name English
PLX-4032
Code English
RO 5185426
Code English
RO-5185426
Code English
VEMURAFENIB [INN]
Common Name English
1-PROPANESULFONAMIDE, N-(3-((5-(4-CHLOROPHENYL)-1H-PYRROLO(2,3-B)PYRIDIN-3- YL)CARBONYL)-2,4-DIFLUOROPHENYL)-
Systematic Name English
VEMURAFENIB [MI]
Common Name English
PLX4032
Code English
RG-7204
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 325310
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
FDA ORPHAN DRUG 444114
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
FDA ORPHAN DRUG 399213
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
EMA ASSESSMENT REPORTS ZELBORAF (AUTHORIZED: MELANOMA)
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
EU-Orphan Drug EU/3/17/1846
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
WHO-VATC QL01XE15
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
LIVERTOX 1024
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
FDA ORPHAN DRUG 529616
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
NCI_THESAURUS C2189
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
FDA ORPHAN DRUG 444314
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
WHO-ATC L01XE15
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
Code System Code Type Description
IUPHAR
5893
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
LactMed
918504-65-1
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
RXCUI
1147220
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY RxNorm
EVMPD
SUB32161
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
NDF-RT
N0000185503
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY P-Glycoprotein Inhibitors [MoA]
PUBCHEM
42611257
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
MERCK INDEX
M11408
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY Merck Index
INN
9286
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
NCI_THESAURUS
C64768
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
ChEMBL
CHEMBL1229517
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
MESH
C551177
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
CAS
918504-65-1
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
HSDB
918504-65-1
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
EPA CompTox
918504-65-1
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
DRUG BANK
DB08881
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
NDF-RT
N0000182138
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY Cytochrome P450 1A2 Inhibitors [MoA]
WIKIPEDIA
VEMURAFENIB
Created by admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
From the human mass balance trial (NP25158), the mean percent of 14 C-vemurafenib related material recovered in feces and urine within 432 hrs pos t-dose was 94.1% and 0.97%, respectively.
FECAL
TRANSPORTER -> INHIBITOR
MDCKII- MDR1 cells.
IC50
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
From the human mass balance trial (NP25158), the mean percent of 14 C-vemurafenib related material recovered in feces and urine within 432 hrs pos t-dose was 94.1% and 0.97%, respectively.
URINE
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
COMPETITIVE INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
MDCKII- MDR1 cells.
IC50
Related Record Type Details
ACTIVE MOIETY
FECAL; URINE
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC