|Systematic (IUPAC) name|
|Licence data||EMA: , US FDA:|
|Pregnancy cat.||X (AU) D (US)|
|Legal status||Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US)|
|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%)|
|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. 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[update]. The drug was developed by the biotechnology / pharmaceutical company Genentech, which is headquartered at South San Francisco, California, USA.
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.
Mechanism of action
The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the hedgehog signaling pathway. SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway. This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.
- Cyclopamine, a naturally occurring SMO antagonist
- "Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients".
- Molecule of the Month. June 2011.
- "FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma".
- "Vismodegib (GDC-0449) Smoothened Inhibitor - BioOncology".
- H. Spreitzer (4 July 2011). "Neue Wirkstoffe – Vismodegib". Österreichische Apothekerzeitung (in German) (14/2011): 10.
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