Vismodegib
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| Pronunciation | /ˌvɪsmoʊˈdɛɡɪb/ VIS-moh-DEG-ib |
| Trade names | Erivedge |
| Synonyms | GDC-0449, RG-3616 |
| AHFS/Drugs.com | Monograph |
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| Routes of administration | By mouth (capsules) |
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| Pharmacokinetic data | |
| Bioavailability | 31.8% |
| Protein binding | >99% |
| Metabolism | <2% metabolised by CYP2C9, CYP3A4, CYP3A5 |
| Biological half-life |
4 days (continuous use), 12 days (single dose) |
| Excretion | Faeces (82%), urine (4.4%) |
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| Formula | C19H14Cl2N2O3S |
| Molar mass | 421.30 g/mol |
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Vismodegib (trade name Erivedge /ˈɛrɪvɛdʒ/ 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.[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
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][4]
Mechanism of action
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]
Side effects
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.[7]
See also
- Cyclopamine, a naturally occurring SMO antagonist
References
- ↑ "Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients".
- 1 2 "Molecule of the Month". June 2011.
- ↑ "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.
- ↑ FDA Professional Drug Information
External links
- Erivedge (vismodegib) Official Web Site
- Efficacy and Safety of Vismodegib
- Food and Drug Administration (FDA) approved vismodegib