ZM 336372

ZM 336372 is a potent, selective ATP-competitive inhibitor of c-Raf in vitro (IC50 = 70 nM for inhibition of human c-Raf). The Ras/Raf-1 signalling pathway is a well-characterized system that links receptor tyrosine kinase (RTK) activation with changes in gene expression and cell behavior. Raf-1 is a serine/threonine protein kinase that phosphorylates and activates MAPK-kinase (MEK) in response to activation by Ras. ZM 336372 also inhibits SAPK2/p38 (IC50 = 2 μM). Selective over 17 other protein kinases including PKA, PKC, p42 MAPK, CDK1 and SAPK1/JNK (up to 50 μM). ZM 336372 causes growth inhibition, suppression of hormone secretion, and up-regulation of cell cycle inhibitors in a human hepatocellular carcinoma cell line.