Vemurafenib

Vemurafenib

Clinical data
Pronunciation	VEM-ue-RAF-e-nib
Trade names	Zelboraf
AHFS/Drugs.com	Monograph
MedlinePlus	a612009
License data	EU EMA: Zelboraf US FDA: Vemurafenib
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	By mouth (tablets)
ATC code	L01XE15 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Identifiers
IUPAC name N-(3-{[5-(4-Chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl}-2,4-difluorophenyl)propane-1-sulfonamide
Synonyms	PLX4032, RG7204, RO5185426
CAS Number	918504-65-1
PubChem CID	42611257
IUPHAR/BPS	5893
DrugBank	DB08881
ChemSpider	24747352 Y
UNII	207SMY3FQT
KEGG	D09996 Y
ChEMBL	CHEMBL1229517
ECHA InfoCard	100.226.540
Chemical and physical data
Formula	C23H18ClF2N3O3S
Molar mass	489.92 g/mol
3D model (Jmol)	Interactive image
SMILES CCCS(=O)(=O)Nc1ccc(F)c(c1F)C(=O)c2c[nH]c3c2cc(cn3)c4ccc(Cl)cc4
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) Y Key:GPXBXXGIAQBQNI-UHFFFAOYSA-N Y

Drug mechanism
Crystallographic structure of B-Raf (rainbow colored, N-terminus = blue, C-terminus = red) complexed with vemurafenib (spheres, carbon = white, oxygen = red, nitrogen = blue, chlorine = green, fluorine = cyan, sulfur = yellow).
Therapeutic use	melanoma
Biological target	BRAF
Mechanism of action	protein kinase inhibitor
External links
ATC code	L01XE15
PDB ligand id	032: PDBe, RCSB PDB
LIGPLOT	3og7

Vemurafenib (INN, marketed as Zelboraf) is a B-Raf enzyme inhibitor developed by Plexxikon (now part of Daiichi-Sankyo) and Genentech for the treatment of late-stage melanoma. The name "vemurafenib" comes from V600E mutated BRAF inhibition.

Vemurafenib received FDA approval for the treatment of late-stage melanoma on August 17, 2011, making it the first drug designed using fragment-based lead discovery to gain regulatory approval.

Vemurafenib later received Health Canada approval on February 15, 2012.

On February 20, 2012, the European Commission approved vemurafenib as a monotherapy for the treatment of adult patients with BRAF V600E mutation positive unresectable or metastatic melanoma, the most aggressive form of skin cancer.

Vemurafenib causes programmed cell death in melanoma cell lines. Vemurafenib interrupts the B-Raf/MEK step on the B-Raf/MEK/ERK pathway − if the B-Raf has the common V600E mutation.

Vemurafenib only works in melanoma patients whose cancer has a V600E BRAF mutation (that is, at amino acid position number 600 on the B-Raf protein, the normal valine is replaced by glutamic acid). About 60% of melanomas have this mutation. It also has efficacy against the rarer BRAF V600K mutation. Melanoma cells without these mutations are not inhibited by vemurafenib; the drug paradoxically stimulates normal BRAF and may promote tumor growth in such cases.