GW 5074 is a potent, selective and cell-permeable c-Raf1 kinase inhibitor (IC50 = 9 nM); displays ≥ 100-fold selectivity for raf kinase over CDK1, CDK2, c-src, ERK2, MEK, p38, Tie2, VEGFR2 and c-fms.
GW5074 is a potent and specific inhibitor of c-Raf with IC50 of 9 nM and has no effect of MKK6, MKK7, p38 MAP kinase and cdks in vitro. However, treatment of neuronal cultures with GW5074 permits accumulation of activating modifications on c-Raf and also B-Raf. The inhibition of LK-induced apoptosis by GW5074 in cerebellar granule neurons is not MEK-ERK-dependent. GW5074 delays down-regulation of Akt activity but inhibits apoptosis by an Akt-independent mechanism. GW5074 affects Ras, nuclear factor-kappa B and c-jun. GW5074 inhibits cell death caused by neurotoxins in granule cells and other neuronal types.
in vivo: GW5074 is protective in an in vivo experimental model of Huntington’s disease. GW5074 (5 mg/Kg) completely prevented extensive bilateral striatal lesions induced by 3-NP in mice. GW5074 suppresses sidestream smoke-induced airway hyperresponsiveness in mice.
For research only, not for human use!
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