In vitro activity: B-Raf IN 1 is a novel, potent and selective B-Raf inhibitor with IC50 of 24 nM; it is equally potent against c-Raf with IC50 of 25 nM. Moderate selectivity was observed for compound 10n versus p38a (IC50: 0.216 lM) and CAMKII (IC50: 0.822 lM), while high selectivity was observed versus CDK2, CDK4, PKCa, IKKb, JNK1, MK2, PKA, Src, MKK6, PLK1, p70S6K, PI3 Ka, and PDK1 (IC50s:>2 lM). It binds to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.

Kinase Assay: B-Raf IN 1 is a novel, potent and selective B-Raf inhibitor with IC50 of 24 nM; it is equally potent against c-Raf with IC50 of 25 nM. Moderate selectivity was observed for compound 10n versus p38a (IC50: 0.216 lM) and CAMKII (IC50: 0.822 lM), while high selectivity was observed versus CDK2, CDK4, PKCa, IKKb, JNK1, MK2, PKA, Src, MKK6, PLK1, p70S6K, PI3 Ka, and PDK1 (IC50s:>2 lM). It binds to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.

Cell Assay: