208260-29-1

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 is a potent ATP-competitive inhibitor of Raf-1 in vitro (IC₅₀ = 70 nM) with the paradoxical effect of inducing >100-fold activation of Raf-1 in whole cells. Activation of the Raf-1 signalling pathway using ZM 336372 in human carcinoid tumor cells results in induction of cell cycle inhibitors and suppression of cellular proliferation.

It is small molecule tyrosine kinase modulator.

ChEBI: 3-(dimethylamino)-N-[3-[[(4-hydroxyphenyl)-oxomethyl]amino]-4-methylphenyl]benzamide is a member of benzamides.

Potent and specific inhibitor of the protein kinase c-Raf (IC50=70nM). Has no significant effect on many other protein kinases tested (even at 50μM) with the exception of p38 (SAPK2a) (IC50=2μM) and SAPK2b (p38β) (IC50=2μM). Induces a paradoxical >100-fold activation of c-Raf in whole cells.

c-Raf: 0.07 μM (IC₅₀, 0.1 mM ATP)

1) Hall-Jackson et al. (1999), Paradoxical activation of Raf by a novel Raf inhibitor; Chem. Biol., 6 559 2) Deming et al. (2010), ZM336372 induces apoptosis associated with phosphorylation of GSK-3beta in pancreatic adenocarcinoma cell lines; J. Surg. Res., 161 28