Clinical data | |
---|---|
Pronunciation |
/ˌvɪsmoʊˈdɛɡɪb/ VIS-moh-DEG-ib |
Trade names | Erivedge |
Other names | GDC-0449, RG-3616 |
AHFS/ Drugs.com | Monograph |
License data |
|
Pregnancy category |
|
Routes of administration | By mouth |
ATC code | |
Legal status | |
Legal status | |
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 | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
ECHA InfoCard | 100.234.019 |
Chemical and physical data | |
Formula | C19H14Cl2N2O3S |
Molar mass | 421.29 g·mol−1 |
3D model ( JSmol) | |
| |
|
Vismodegib, sold under the brand name Erivedge, is a medication used for the treatment of basal-cell carcinoma (BCC). [3] 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. [4] 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 [update]. [5] The drug was developed by the biotechnology/ pharmaceutical company Genentech. [4]
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. [4] [6]
The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway. [5] SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway. [7] This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas. [8]
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). [3]
Vismodegib has undergone several promising phase I and phase II clinical trials for its use in treating medulloblastoma. [9]