Vismodegib

Vismodegib

Systematic (IUPAC) name
2-Chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide
Clinical data
Trade names	Erivedge
AHFS/Drugs.com	monograph
Licence data	EMA:Link, US FDA:link
Pregnancy category	AU: X (High risk) US: D (Evidence of risk)
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral
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%)
Identifiers
CAS Number	879085-55-9
ATC code	L01XX43
PubChem	CID 24776445
IUPHAR/BPS	6975
DrugBank	DB08828
ChemSpider	23337846
UNII	25X868M3DS
ChEBI	CHEBI:66903
ChEMBL	CHEMBL473417
Synonyms	GDC-0449, RG-3616
Chemical data
Formula	C19H14Cl2N2O3S
Molar mass	421.30 g/mol
SMILES CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl
InChI InChI=1S/C19H14Cl2N2O3S/c1-27(25,26)13-6-7-14(17(21)11-13)19(24)23-12-5-8-16(20)15(10-12)18-4-2-3-9-22-18/h2-11H,1H3,(H,23,24) Key:BPQMGSKTAYIVFO-UHFFFAOYSA-N

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] [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

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

External links

• Erivedge® (vismodegib), a prescription oral medica on approved for advanced basal cell carcinoma treatment
• Efficacy and Safety of Vismodegib
• Food and Drug Administration (FDA) approved vismodegib