Raf Inhibitors

The present Competitive Intelligence Report about Raf inhibitors provides a competitor evaluation in the field of synthetic molecules targeting Raf and mutant Raf (V600E) for treatment of cancer as of May 2009.

The mitogen activated protein kinases (MAPKs) are conserved proteins that regulate cell growth, division and death. Although activated in the cytosol, the MAPKs translocate to the nucleus upon activation and phosphorylate a large number of nuclear proteins. Investigating how Ras transmits extracellular growth signals, the MAPK pathway has emerged as the crucial route between membrane-bound Ras and the nucleus. The MAPK pathway represents a cascade of phosphorylation events including three pivotal kinases, namely Raf, MEK (MAP kinase kinase), and ERK (MAP kinase). These kinases present new opportunities for the development of target-specific and probably less toxic anti-tumor agents.

It has been reported that BRAF kinase is one of the most frequently mutated members of the kinase family across all cancers, and is causative of about 60 % of malignant melanomas, 40-50% of colorectal cancer, and thyroid cancers. The V600E mutant form of BRAF kinase is the dominant activating, dysregulated mutation of BRAF in these cancers. While the first generation of B-Raf kinase inhibitors has reached the market or is in advanced clinical development, these inhibitors were rather unspecific or multikinase inhibitors. Nexavar (sorafenib) was shown to inhibit multiple intracellular (C-RAF, B-RAF and mutant B-RAF) and cell surface kinases (KIT, FLT-3, RET, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-). The newer generation of B-Raf kinase inhibitors selectively are targeting the B-Raf V600E mutation. Several programs are in early clinical development and quite a number of inhibitors in preclinical R&D.

The report includes a compilation of current active products and projects in research and development of multikinase and selective Raf kinase inhibitors. In addition, the report lists company-specific R&D pipelines of Raf kinase targeting molecules. Competitor projects are listed in a tabular format providing information on:

• Drug Codes,
• Target / Mechanism of Action,
• Class of Compound,
• Company,
• Product Category,
• Indication,
• R&D Stage and
• additional comments with a hyperlink leading to the source of information.