Description
GW-5074 (220904-83-6) is a potent inhibitor of cRAF1 kinase (IC50 = 9 nM). Displays 100-fold selectivity for cRAF1 over CDK1, CDK2, c-src, ERK2, MEK, p38, Tie2, VEGFR2 and c-fm. GW-5074 displays neuroprotective effects in vivo via a mechanism that is independent of MEK, ERK, and Akt signaling. Cell permeable.
Uses
Potent and selective cell permeable inhibitor of cRAF1 kinase (IC50 = 9 nM) with 100-fold selectivity over CDK1, CDK2, c-src, ERK2, MEK, p38, Tie2, VEGFR2 and c-fm. A useful tool for assessing the involvement of the Ras/Raf-1/ERK pathway in various signaling pathways. Displays neuroprotective effects in vivo through a MEK-ERK and Akt-independent mechanism.
Uses
Potent Raf1 kinase inhibitor (IC50=9nM). Shows ≥100-fold selectivity for Raf kinase versus CDK1, CDK2, c-Src, ERK2, MEK, p38, Tie2, VEGFR2, and c-Fms.
Biological Activity
Potent, selective and cell-permeable c-Raf1 kinase inhibitor (IC 50 = 9 nM). Displays ≥ 100-fold selectivity for raf kinase over CDK1, CDK2, c-src, ERK2, MEK, p38, Tie2, VEGFR2 and c-fm.
Biochem/physiol Actions
GW5074 is a cRaf1 kinase inhibitor, which is placed immediately downstream of Ras in the Motogen activated protein kinase (MAPK) signaling pathway. It elicits protection in GW5074 prevents degeneration in Huntington′s disease and also have therapeutic potential in treating neurodegenerative disorders. GW5074 in combination with anti-inflammatory drug, dexamethasone, attenuates sidestream smoke-induced airway inflammation.
References
1) Chang et al. (2005), Phorbol 12-myristate 13-acetate upregulates cyclooxygenase-2 expression in human pulmonary epithelial cells via Ras, Raf-1, ERK, and NF-kappaB, but not p38 MAPK pathways; Cell Signal., 217 299
2) Huang et al. (2006), Fibroblast growth factor-2 suppresses oridonin-induced L929 apoptosis through extracellular signal-regulated kinase-dependent and phosphatidylinositol 3-kinase-independent pathway; J. Pharmacol. Sci., 102 305
3) Lackey et al. (2000), The discovery of potent cRaf1 kinase inhibitors; Bioorg. Med. Chem. Lett., 10 223
4) Chen et al. (2004), Bradykinin B2 receptor mediates NF-kappaB activation and cyclooxygenase-2 expression via the Ras/Raf-1/ERK pathway in human airway epithelial cells; J. Immunol., 173 5219
