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Vemurafenib structure.svg
Vemurafenib ball-and-stick model.png
Pronunciation/ˌvɛməˈræfənɪb/ VEM-ə-RAF-ə-nib
Trade namesZelboraf
Other namesPLX4032, RG7204, RO5185426
  • N-(3-{[5-(4-Chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl}-2,4-difluorophenyl)propane-1-sulfonamide
Clinical data
Drug classBRAF kinase inhibitor[1]
Main usesMelanoma, Erdheim-Chester disease[2]
Side effectsJoint pain, hair loss, itchiness, QT prolongation, tiredness[2]
  • AU: D
  • US: D (Evidence of risk)
Routes of
By mouth (tablets)
Typical dose960 mg twice per day[2]
External links
License data
Legal status
Chemical and physical data
Molar mass489.92 g·mol−1
3D model (JSmol)
  • CCCS(=O)(=O)Nc1ccc(F)c(c1F)C(=O)c2c[nH]c3c2cc(cn3)c4ccc(Cl)cc4
  • 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) checkY

Vemurafenib, sold under the brand name Zelboraf, is a medication used to treat certain types of late-stage melanoma and Erdheim-Chester disease.[2] Specifically it is used in those with a BRAF V600E mutation.[2] It is taken by mouth.[2]

Common side effects include joint pain, hair loss, itchiness, QT prolongation, and tiredness.[2] Other side effects may include Dupuytren contracture, sensitivity to radiation therapy, eye inflammation, liver problems, and a new cancer.[2] Use in pregnancy may harm the baby.[2] It works by blocking the b-Raf enzyme.[2]

Vemurafenib was approved for medical use in the United States in 2011 and Europe in 2012.[2][3] In the United Kingdom 56 tablets of 240 mg costs the NHS about £1,750 as of 2021.[1] This amount in the United States costs about 2,650 USD.[4]

Medical uses

It is used for melanoma and some people with Erdheim–Chester disease (ECD), a rare type of histiocytic neoplasm.[5][6]


It is generally taken at a dose of 960 mg twice per day.[2] Though smaller doses may be used in those in who side effects are too great.[2]

Side effects

At the maximum tolerated dose (MTD) of 960 mg twice a day 31% of patients get skin lesions that may need surgical removal.[7] The BRIM-2 trial investigated 132 patients; the most common adverse events were arthralgia in 58% of patients, skin rash in 52%, and photosensitivity in 52%. In order to better manage side effects some form of dose modification was necessary in 45% of patients. The median daily dose was 1750 mg, 91% of the MTD.[8]

A trial combining vemurafenib and ipilimumab was stopped in April 2013 because of signs of liver toxicity.[9]

Mechanism of action

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).[7]
Therapeutic usemelanoma
Biological targetBRAF
Mechanism of actionprotein kinase inhibitor
External links
ATC codeL01XE15
PDB ligand id032: PDBe, RCSB PDB

Vemurafenib causes programmed cell death in melanoma cell lines.[10] 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).[11] 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.[12][13]


Three mechanisms of resistance to vemurafenib (covering 40% of cases) have been discovered:

Society and culture


Vemurafenib received FDA approval for the treatment of late-stage melanoma on August 17, 2011,[17] making it the first drug designed using fragment-based lead discovery to gain regulatory approval.[18]

Vemurafenib later received Health Canada approval on February 15, 2012.[19]

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.[20]


The name "vemurafenib" comes from V600E mutated BRAF inhibition.


In a phase I clinical study, vemurafenib (then known as PLX4032) was able to reduce numbers of cancer cells in over half of a group of 16 patients with advanced melanoma. The treated group had a median increased survival time of 6 months over the control group.[21][22][23][24]

A second phase I study, in patients with a V600E mutation in B-Raf, ~80% showed partial to complete regression. The regression lasted from 2 to 18 months.[25]

In early 2010 a Phase I trial[26] for solid tumors (including colorectal cancer), and a phase II study (for metastatic melanoma) were ongoing.[27]

A phase III trial (vs dacarbazine) in patients with previously untreated metastatic melanoma showed an improved rates of overall and progression-free survival.[28]

In June 2011, positive results were reported from the phase III BRIM3 BRAF-mutation melanoma study.[29] The BRIM3 trial reported good updated results in 2012.[30]

Further trials are planned including a trial of vemurafenib co-administered with GDC-0973 (cobimetinib), a MEK-inhibitor.[29] After good results in 2014 the combination was submitted to the EC and FDA for marketing approval.[31]

In January 2015 trial results compared vemurafenib with the combination of dabrafenib and trametinib for metastatic melanoma.[32]


  1. 1.0 1.1 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 1062. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 "Vemurafenib Monograph for Professionals". Archived from the original on 4 March 2021. Retrieved 13 September 2021.
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  6. Diamond, Eli L.; Subbiah, Vivek; Lockhart, A. Craig; Blay, Jean-Yves; Puzanov, Igor; Chau, Ian; Raje, Noopur S.; Wolf, Jurgen; Erinjeri, Joseph P. (2018-03-01). "Vemurafenib for BRAF V600-Mutant Erdheim–Chester Disease and Langerhans Cell Histiocytosis: Analysis of Data From the Histology-Independent, Phase 2, Open-label VE-BASKET Study". JAMA Oncology. 4 (3): 384–388. doi:10.1001/jamaoncol.2017.5029. ISSN 2374-2445. PMC 5844839. PMID 29188284.
  7. 7.0 7.1 PDB: 3OG7​; Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, Spevak W, Zhang C, Zhang Y, Habets G, et al. (September 2010). "Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma". Nature. 467 (7315): 596–599. Bibcode:2010Natur.467..596B. doi:10.1038/nature09454. PMC 2948082. PMID 20823850.
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Further reading

External links

External sites: