Vismodegib
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.[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]
Development
Vismodegib has undergone several promising phase I and phase II clinical trials for its use in treating medulloblastoma.[8]
References
- "Erivedge® (vismodegib)". Australian Prescribing Information, Australian Register of Therapeutic Goods (ARTG). Roche Products Pty Limited. 17 November 2022.
- "Erivedge- vismodegib capsule". DailyMed. U.S. National Library of Medicine. 9 April 2019. Retrieved 8 January 2023.
- "FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma". Roche. 30 January 2012. Retrieved 9 August 2020.
- "Vismodegib". Molecule of the Month. Prous Science. June 2011. Archived from the original on 27 September 2011.
- Lacroix M (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7. Archived from the original on 2015-06-26. Retrieved 2014-07-13.
- "Vismodegib (GDC-0449) Smoothened Inhibitor". BioOncology. Genentech. Archived from the original on 4 June 2011.
- Spreitzer H (4 July 2011). "Neue Wirkstoffe – Vismodegib". Österreichische Apothekerzeitung (in German) (14/2011): 10.
- Li Y, Song Q, Day BW (July 2019). "Phase I and phase II sonidegib and vismodegib clinical trials for the treatment of paediatric and adult MB patients: a systemic review and meta-analysis". Acta Neuropathologica Communications. 7 (1): 123. doi:10.1186/s40478-019-0773-8. PMC 6668073. PMID 31362788.
Further reading
- Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, et al. (June 2012). "Efficacy and safety of vismodegib in advanced basal-cell carcinoma". The New England Journal of Medicine. 366 (23): 2171–2179. doi:10.1056/NEJMoa1113713. PMC 5278761. PMID 22670903.
External links
- "Vismodegib". Drug Information Portal. U.S. National Library of Medicine.