MedKoo product information:

BIX02188

Description of BIX02188: BIX02188 is a MEK5 inhibitor which inhibits catalytic function of purified, MEK5 enzyme. The MEK5 inhibitor blocked phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells. BIX02188 also inhibited transcriptional activation of MEF2C, a downstream substrate of the MEK5/ERK5 signaling cascade, in a cellular trans-reporter assay system. These inhibitors offer novel pharmacological tools to better characterize the role of the MEK5/ERK5 pathway in various biological systems. (source: Biochem Biophys Res Commun. 2008 Dec 5;377(1):120-5. Epub 2008 Oct 1.).

Current developer:    Boehringer Ingelheim Pharmaceuticals, Inc.

BIX02188 is a novel MEK5 inhibitor, which inhibited catalytic function of purified, MEK5 enzyme. The MEK5 inhibitors blocked phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells. The compds. also inhibited transcriptional activation of MEF2C, a downstream substrate of the MEK5/ERK5 signaling cascade, in a cellular trans-reporter assay system. This inhibitors offer novel pharmacol. tools to better characterize the role of the MEK5/ERK5 pathway in various biol. systems.

1: Obara Y, Nakahata N. The signaling pathway leading to extracellular signal-regulated kinase 5 (ERK5) activation via G-proteins and ERK5-dependent neurotrophic effects. Mol Pharmacol. 2010 Jan;77(1):10-6. Epub 2009 Oct 26. Review. PubMed PMID: 19858097.

2: Obara Y, Yamauchi A, Takehara S, Nemoto W, Takahashi M, Stork PJ, Nakahata N. ERK5 activity is required for nerve growth factor-induced neurite outgrowth and stabilization of tyrosine hydroxylase in PC12 cells. J Biol Chem. 2009 Aug 28;284(35):23564-73. Epub 2009 Jul 6. PubMed PMID: 19581298; PubMed Central PMCID: PMC2749131.

3: Tatake RJ, O'Neill MM, Kennedy CA, Wayne AL, Jakes S, Wu D, Kugler SZ Jr, Kashem MA, Kaplita P, Snow RJ. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun. 2008 Dec 5;377(1):120-5. Epub 2008 Oct 1. PubMed PMID: 18834865.

4: Li L, Tatake RJ, Natarajan K, Taba Y, Garin G, Tai C, Leung E, Surapisitchat J, Yoshizumi M, Yan C, Abe J, Berk BC. Fluid shear stress inhibits TNF-mediated JNK activation via MEK5-BMK1 in endothelial cells. Biochem Biophys Res Commun. 2008 May 23;370(1):159-63. Epub 2008 Mar 19. PubMed PMID: 18358237; PubMed Central PMCID: PMC2435412.