Vismodegib (trade name Erivedge // ERR-i-vej) 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.
|By mouth (capsules)|
|Metabolism||<2% metabolised by CYP2C9, CYP3A4, CYP3A5|
|Elimination half-life||4 days (continuous use),|
12 days (single dose)
|Excretion||Fecal (82%), Urinary (4.4%)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||421.30 g/mol g·mol−1|
|3D model (JSmol)|
Mechanism of actionEdit
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.
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.
- Cyclopamine, a naturally occurring SMO antagonist
- FDA Professional Drug Information
- "Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients".
- "Molecule of the Month". June 2011. Cite journal requires
- "FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma".
- Lacroix, Marc (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7.
- "Vismodegib (GDC-0449) Smoothened Inhibitor - BioOncology".
- H. Spreitzer (4 July 2011). "Neue Wirkstoffe – Vismodegib". Österreichische Apothekerzeitung (in German) (14/2011): 10.