Vismodegib
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|---|---|
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| Systematic (IUPAC) name | |
| 2-Chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide | |
| Clinical data | |
| Trade names | Erivedge |
| AHFS/Drugs.com | entry |
| Licence data | US FDA:link |
| Pregnancy cat. | D (US) |
| Legal status | ℞-only (US) |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | 31.8% (single dose), saturable |
| Protein binding | > 99% |
| Metabolism | <2% metabilised by CYP2C9, CYP3A4, CYP3A5 |
| Half-life | 4 days (continuous use), 12 days (single dose) |
| Excretion | Mainly unchanged; 82% hepatic, 4% renal |
| Identifiers | |
| CAS number | 879085-55-9 |
| ATC code | L01XX43 |
| PubChem | CID 24776445 |
| ChemSpider | 23337846 |
| UNII | 25X868M3DS |
| ChEBI | CHEBI:66903  |
| ChEMBL | CHEMBL473417 |
| Synonyms | GDC-0449, RG-3616 |
| Chemical data | |
| Formula | C19H14Cl2N2O3S |
| Mol. mass | 421.30 g/mol |
| SMILES
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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
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
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
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
- Cyclopamine, a naturally occurring SMO antagonist
References
- ↑ "Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients".
- ↑ 2.0 2.1 Molecule of the Month. June 2011.
- ↑ "FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma".
- ↑ FDA Professional Drug Information
- ↑ "Vismodegib (GDC-0449) Smoothened Inhibitor - BioOncology".
- ↑ H. Spreitzer (4 July 2011). "Neue Wirkstoffe – Vismodegib". Österreichische Apothekerzeitung (in German) (14/2011): 10.