XL281 (BMS-908662) is being investigated to selectively target RAF kinases including B-RAF, C-RAF and the B-RAF mutant (V600E).1 RAF is a cytoplasmic serine/threonine protein kinase that is a direct down-stream effector of the RAS GTPase, and is an important component in the RAS/RAF/MEK/ERK (MAPK) signaling pathway. This pathway functions to transmit growth and survival signals from cell surface receptors and cytoplasmic signaling elements to the nucleus.2 Signal transduction through this pathway plays an important role in the proliferation and survival of tumor cells.2
Out-licensed to BMS.
- Malek S., et al. Selective inhibition of RAF results in downregulation of the RAS/RAF/MEK/ERK pathway and inhibition of tumor growth in vivo. Eur. J. Cancer Suppl. 2006; 4: 184.
- Beeram M, Patnaik A, Rowinsky EK. Raf: A strategic target for therapeutic development against cancer. J Clin Oncol. 2005; 23(27):6771-6790.