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Tag Archives: GDC-0449
Erivedge , Vismodegib
The molecule also is known as GDC-0449 and RG3616.
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Vismodegib works by interfering with the membrane protein Smoothened, which provides positive signals to the Hh pathway. At present, there are no FDA-approved drugs targeting Hh signaling, although the pathway is the focus of investigation in a variety of cancers.
Meantime, Roche has obtained conditional European approval for Erivedge (vismodegib) for the treatment of adults with symptomatic metastatic basal cell carcinoma (BCC) or locally advanced BCC inappropriate for surgery or radiotherapy.
The Basel-based group noted that the approval makes Erivedge, a capsule taken once-a-day, the first licensed medicine for patients in the European Union “with this disfiguring and potentially life-threatening form of skin cancer”. Chief medical officer Hal Barron said the green light “is great news for patients with advanced basal cell carcinoma, who previously had no medicines to treat their disease”, adding that Erivedge substantially reduced tumour size in patients in clinical trials.
Under the conditional approval, Roche will provide additional data from an ongoing global safety study. Erivedge was approved by the US Food and Drug Administration in January 2012 following a priority review.
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. The drug is also undergoing clinical trials for metastatic colorectal cancer,small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastomaand chondrosarcoma as of June 2011. The drug was developed by the biotechnology /pharmaceutical company Genentech, which is headquartered at South San Francisco, California, USA.
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.
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.
- “Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients”.
- Molecule of the Month. June 2011.
- “FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma”.
- “Vismodegib (GDC-0449) Smoothened Inhibitor – BioOncology”.
- H. Spreitzer (4 July 2011). “Neue Wirkstoffe – Vismodegib”. Österreichische Apothekerzeitung (in German) (14/2011): 10.
Vismodegib is Hedgehog (Hg) path inhibitors. Pka = 3.8 (pyridinium cation); soluble 0.1μg/mL (pH = 7), 0.99mg/mL (pH = 1), logP = 2.7. Vismodegib can be synthesized by the following route: