Vismodegib

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.[2] 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.[3] The drug was developed by the biotechnology/pharmaceutical company Genentech, which is headquartered at South San Francisco, California, USA.

Vismodegib
Clinical data
Pronunciation/ˌvɪsmoʊˈdɛɡɪb/ VIS-moh-DEG-ib
Trade namesErivedge
Other namesGDC-0449, RG-3616
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: X (High risk) [1]
  • US: X (Contraindicated) [1]
    Routes of
    administration    		By mouth (capsules)
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability31.8%
    Protein binding>99%
    Metabolism<2% metabolised by CYP2C9, CYP3A4, CYP3A5
    Elimination half-life4 days (continuous use),
    12 days (single dose)
    ExcretionFecal (82%), Urinary (4.4%)
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.234.019
    Chemical and physical data
    FormulaC19H14Cl2N2O3S
    Molar mass421.30 g/mol g·mol−1
    3D model (JSmol)

    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.[4][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.[3] 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 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.[1]

    See also
    • Cyclopamine, a naturally occurring SMO antagonist

    References
    1. FDA Professional Drug Information
    2. "Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients".
    3. "Molecule of the Month". June 2011. Cite journal requires |journal= (help)
    4. "FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma".
    5. Lacroix, Marc (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7.
    6. "Vismodegib (GDC-0449) Smoothened Inhibitor - BioOncology".
    7. H. Spreitzer (4 July 2011). "Neue Wirkstoffe – Vismodegib". Österreichische Apothekerzeitung (in German) (14/2011): 10.
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