RAF265

An oral, highly selective, and potent RAF and VEGFR kinase inhibitor

Raf is a key component of the Ras-Raf-MEK-ERK signal-transduction pathway, which controls cell proliferation, differentiation, and apoptosis in mammalian cells, and may play a key role in many cancers. Mutation and overexpression of components of the pathway are common in various cancers. There are 3 isoforms of Raf: A-Raf, B-Raf, and C-Raf.¹ Activating mutations of B-Raf have been identified in multiple cancers, especially malignant melanoma (B-Raf V600E). In addition, Ras is often mutated to an oncogenic form in many solid tumors and hematologic malignancies.²

RAF265 is a potent inhibitor of Raf with a highly selective profile. Preclinical research has shown that RAF265 inhibits all 3 isoforms of Raf, as well as mutant B-Raf, with high potency. In addition, RAF265 has antiangiogenic activity through inhibition of VEGFR-2. Antitumor activity of RAF265 has been seen in preclinical xenograft models.³

RAF265 is now being investigated in Phase I clinical trials in malignant melanoma.

All compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.

1. Beeram M, Patnaik A, Rowinsky EK. Raf: a strategic target for therapeutic development against cancer. J Clin Oncol. 2005;23:6771-6790.
2. Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Nat Acad Sci. 2004;101:13489-13494.
3. Schmidt-Arras D-E, Bohmer A, Markova B, Choudhary C, Serve H, Bohmer F-D. Tyrosine phosphorylation regulates maturation of receptor tyrosine kinases. Mol Cell Biol. 2005;25:3690-3703.