GW-5074

• CAT Number: I002692
• CAS Number: 220904-83-6
• Molecular Formula: C₁₅H₈Br₂INO₂
• Molecular Weight: 520.95
• Purity: ≥95%
• Target: Raf
• Solubility: 10 mM in DMSO
• Storage: 3 years -20C powder
• IC50: 9 nM [1]
• InChI: InChI=1S/C15H8Br2INO2/c16-11-4-7(5-12(17)14(11)20)3-10-9-6-8(18)1-2-13(9)19-15(10)21/h1-6,20H,(H,19,21)/b10-3-
• InChIKey: LMXYVLFTZRPNRV-KMKOMSMNSA-N
• SMILES: C1=CC2=C(C=C1I)C(=CC3=CC(=C(C(=C3)Br)O)Br)C(=O)N2

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.IC50 value: 9 nM [1]Target: 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 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 [1]. GW5074 suppresses sidestream smoke-induced airway hyperresponsiveness in mice [2].

Reference

1:Intrathecal delivery of farnesyl thiosalicylic acid and GW 5074 attenuates hyperalgesia and allodynia in chronic constriction injury-induced neuropathic pain in rats. Jaggi AS, Singh N.Neurol Sci. 2013 Mar;34(3):297-304. doi: 10.1007/s10072-012-0991-3. Epub 2012 Mar 2. PMID: 22382741 2:Analgesic potential of intrathecal farnesyl thiosalicylic acid and GW 5074 in vincristine-induced neuropathic pain in rats. Jaggi AS, Singh N.Food Chem Toxicol. 2012 May;50(5):1295-301. doi: 10.1016/j.fct.2012.01.038. Epub 2012 Feb 4. PMID: 22326968