Dabrafenib

Dabrafenib (GSK2118436A) is a potent ATP-competitive inhibitor of B-Raf, B-Raf V600E and c-Raf with IC50 of 3.2 nM, 0.8 nM and 5.0 nM, respectively. Dabrafenib is selective for Raf kinase, with 400 fold selectivity towards B-Raf over 91% of the other kinases tested. Dabrafenib (orally administrated) inhibits the growth of B-RafV600E mutant melanoma (A375P) and colon cancer (Colo205) human tumor xenografts, growing subcutaneously in immuno-compromised mice. GSK2118436 treatment results in no detectable negative impact on existing systemic immunity or the de novo generation of tumor-specific T cells. Dabrafenib (GSK2118436A) is currently in phase III clinical trial in patients with melanoma.