ZM 336372

Description

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.

Uses

It is small molecule tyrosine kinase modulator. ZM336372 induces apoptosis associated with phosphorylation of GSK-3β in pancreatic adenocarcinoma cell lines.

Definition

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

IC 50

c-Raf: 0.07 μM (IC₅₀, 0.1 mM ATP)

References

[1] C A HALL-JACKSON. Paradoxical activation of Raf by a novel Raf inhibitor.[J]. Chemistry & biology, 1999, 6 8: 559-568. DOI:10.1016/s1074-5521(99)80088-x
[2] DUSTIN DEMING M.D. . ZM336372 Induces Apoptosis Associated with Phosphorylation of GSK-3β in Pancreatic Adenocarcinoma Cell Lines[J]. Journal of Surgical Research, 2010, 161 1: Pages 28-32. DOI:10.1016/j.jss.2009.06.013