Vismodegib
Chemical compound
From Wikipedia, the free encyclopedia
Vismodegib, sold under the brand name Erivedge, is a medication used for the treatment of basal-cell carcinoma (BCC).[2] 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.[3] 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].[4] The drug was developed by the biotechnology/pharmaceutical company Genentech.[3]
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| Pronunciation | /ˌvɪsmoʊˈdɛɡɪb/ VIS-moh-DEG-ib |
| Trade names | Erivedge |
| Other names | GDC-0449, RG-3616 |
| AHFS/Drugs.com | Monograph |
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| Routes of administration | By mouth |
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| Bioavailability | 31.8% |
| Protein binding | >99% |
| Metabolism | <2% metabolised by CYP2C9, CYP3A4, CYP3A5 |
| Elimination half-life | 4 days (continuous use), 12 days (single dose) |
| Excretion | Fecal (82%), Urinary (4.4%) |
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| ECHA InfoCard | 100.234.019 |
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| Formula | C19H14Cl2N2O3S |
| Molar mass | 421.29 g·mol−1 |
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Indication
Vismodegib is indicated for people 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][5]
Mechanism of action
The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway.[4] SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway.[6] This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.[7]
Side effects
In clinical trials, common side effects included gastrointestinal disorders (nausea, vomiting, diarrhoea, constipation), muscle spasms, fatigue, hair loss, and dysgeusia (distortion of the sense of taste).[2]
