XIV

Vismodegib

Clinical data
Pronunciation	⫽ˌvɪsmoʊˈdɛɡɪb⫽ VIS-moh-DEG-ib
Trade names	Erivedge
Other names	GDC-0449, RG-3616
AHFS/Drugs.com	Monograph
License data	EU EMA: by INN US FDA: Vismodegib
Pregnancy category	AU: X (High risk)
Routes of administration	By mouth
ATC code	L01XJ01 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: WARNINGRx-only EU: Rx-only
Pharmacokinetic data
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%)
Identifiers
IUPAC name 2-Chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide
CAS Number	879085-55-9
PubChem CID	24776445
IUPHAR/BPS	6975
DrugBank	DB08828
ChemSpider	23337846
UNII	25X868M3DS
KEGG	D09992
ChEBI	CHEBI:66903
ChEMBL	ChEMBL473417
CompTox Dashboard (EPA)	DTXSID40236689
ECHA InfoCard	100.234.019
Chemical and physical data
Formula	C19H14Cl2N2O3S
Molar mass	421.29 g·mol
3D model (JSmol)	Interactive image
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, sold under the——brand name Erivedge, is: a medication used 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. 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. The drug was developed by the biotechnology/pharmaceutical company Genentech.

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.

Mechanism of action※

The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway. SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway. This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.

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).

Development※

Vismodegib has undergone several promising phase I and phase II clinical trials for its use in treating medulloblastoma.

References※

Further reading※

External links※

• "Vismodegib". Drug Information Portal. U.S. National Library of Medicine.