Chapter Twenty-Six - Case History: Vemurafenib, a Potent, Selective, and First-in-Class Inhibitor of Mutant BRAF for the Treatment of Metastatic Melanoma

Abstract BRAF oncogene is found in about half of all metastatic melanoma and several other cancers. This druggable target presents the opportunity to develop oncogene-selective inhibitors that could be beneficial to melanoma patients. Vemurafenib (PLX4032) was discovered as part of a series of orally available, mutant-selective, BRAF inhibitors using “scaffold-based drug discovery” platform, which employs early co-crystallography to enhance the screening and chemistry optimization paradigm. Following a rapid clinical development path, vemurafenib was approved in the United States in 2011 and the European Union in 2012 and is marketed as Zelboraf® for the treatment of unreseactable or metastatic melanoma with BRAF V600E mutation as detected by an US Food and Drug Administration approved test.