Vismodegib

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Vismodegib
Vismodegib2DACS.svg
Vismodegib3Dan.gif
Systematic (IUPAC) name
2-Chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide
Clinical data
Trade names Erivedge
AHFS/Drugs.com monograph
Licence data EMA:Link, US FDA:link
Pregnancy cat. X (AU) D (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 31.8%
Protein binding > 99%
Metabolism <2% metabolised by CYP2C9, CYP3A4, CYP3A5
Half-life 4 days (continuous use),
12 days (single dose)
Excretion Faeces (82%), urine (4.4%)
Identifiers
CAS number 879085-55-9
ATC code L01XX43
PubChem CID 24776445
DrugBank DB08828
ChemSpider 23337846
UNII 25X868M3DS
ChEBI CHEBI:66903 YesY
ChEMBL CHEMBL473417
Synonyms GDC-0449, RG-3616
Chemical data
Formula C19H14Cl2N2O3S 
Mol. mass 421.30 g/mol

Vismodegib (trade name Erivedge) is a drug for the treatment of basal-cell carcinoma (BCC). The approval of vismodegib on January 30, 2012, represents the first Hedgehog signaling pathway targeting agent to gain U.S. Food and Drug Administration (FDA) approval.[1] The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma as of June 2011.[2] The drug was developed by the biotechnology / pharmaceutical company Genentech, which is headquartered at South San Francisco, California, USA.

Indication[edit]

Vismodegib is indicated for patients with basal cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation.[3]

Side effects[edit]

In clinical trials, common adverse effects included gastrointestinal disorders (nausea, vomiting, diarrhoea, constipation), muscle spasms, fatigue, hair loss, and dysgeusia (distortion of the sense of taste). The effects were mostly mild to moderate.[4]

Mechanism of action[edit]

The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the hedgehog signaling pathway.[2] SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway.[5] This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.[6]

See also[edit]

References[edit]

Pyridyl Inhibitors of Hedgehog Signalling WO 2006028958 A2 PCT/US2005/031284 CA2579002A1, CA2579002C, CN101072755A, CN102964294A, EP1789390A2, EP1789390B1, US7888364, US20060063779, US20110092461, Inventors: Janet Gunzner, Daniel Sutherlin, Mark Stanley, Liang Bao, Georgette Castanedo, Rebecca Lalonde, Shumei Wang, Mark Reynolds, Scott Savage, Kimberly Malesky, Michael Dina