TAK-632 is a slow off-rate inhibitor of Raf kinases (IC50s = 8.3, 2.4, and 1.4 nM for wild type B-Raf, mutant B-RafV600E, and c-Raf, respectively). It demonstrates 14-1,200-fold selectivity for Raf over a panel of 26 different kinases. TAK-632 shows significant antiproliferative activity against mutated B-Raf or mutated N-Ras cancer cell lines and xenograft models, inhibiting MEK phosphorylation with an IC50 value of 12 nM and downstream ERK phosphorylation with an IC50 value of 16 nM.
