tcsc0092 GW 5074

GW 5074 is a potent and selective c-Raf inhibitor with IC₅₀ of 9 nM, and has no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms.

IC50 & Target: IC50: 9 nM (c-Raf)

In Vitro: 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^[1].

In Vivo: GW5074 (5 mg/Kg) completely prevents extensive bilateral striatal lesions induced by 3-NP in mice^[1]. GW5074 suppresses sidestream smoke-induced airway hyperresponsiveness in mice^[2]. GW5074 completely abolishes chronic morphine-mediated AC superactivation I in CHO cells stably expressing the humanμ-opioid receptor^[3].