VX-745

• CAT Number: I002609
• CAS Number: 209410-46-8
• Molecular Formula: C₁₉H₉Cl₂F₂N₃OS
• Molecular Weight: 436.26
• Purity: ≥95%
• Target: p38
• Solubility: DMSO ≥60mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL
• Storage: -20°C
• IC50: 10 nM
• IUPAC Name: 5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one
• InChI: InChI=1S/C19H9Cl2F2N3OS/c20-11-2-1-3-12(21)17(11)18-14-5-7-16(25-26(14)9-24-19(18)27)28-15-6-4-10(22)8-13(15)23/h1-9H
• InChIKey: VEPKQEUBKLEPRA-UHFFFAOYSA-N
• SMILES: C1=CC(=C(C(=C1)Cl)C2=C3C=CC(=NN3C=NC2=O)SC4=C(C=C(C=C4)F)F)Cl

VX-745（Cat No.:I002609） is a highly potent and selective inhibitor of p38α, a member of the mitogen-activated protein kinase (MAPK) family. It displays an impressive IC50 value of 10 nM, indicating strong inhibition of p38α activity. Importantly, VX-745 exhibits 22-fold greater selectivity towards p38α compared to p38β, another isoform of p38 MAPK. Notably, it does not inhibit p38γ, further highlighting its specificity. This selectivity profile makes VX-745 a valuable tool for studying p38α-mediated signaling pathways and potential therapeutic applications targeting this kinase.

Reference

1:The Discovery of VX-745: A Novel and Selective p38α Kinase Inhibitor. Duffy JP, Harrington EM, Salituro FG, Cochran JE, Green J, Gao H, Bemis GW, Evindar G, Galullo VP, Ford PJ, Germann UA, Wilson KP, Bellon SF, Chen G, Taslimi P, Jones P, Huang C, Pazhanisamy S, Wang YM, Murcko MA, Su MS.ACS Med Chem Lett. 2011 Jul 28;2(10):758-63. doi: 10.1021/ml2001455. eCollection 2011 Oct 13. PMID: 24900264 Free PMC Article2:Gram-scale synthesis of the p38α MAPK-inhibitor VX-745 for preclinical studies into Werner syndrome. Bagley MC, Davis T, Dix MC, Fusillo V, Pigeaux M, Rokicki MJ, Kipling D.Future Med Chem. 2010 Sep;2(9):1417-27. doi: 10.4155/fmc.10.217. PMID: 21426137 3:Microwave-assisted Ullmann C-S bond formation: synthesis of the P38alpha MAPK clinical candidate VX-745. Bagley MC, Davis T, Dix MC, Fusillo V, Pigeaux M, Rokicki MJ, Kipling D.J Org Chem. 2009 Nov 6;74(21):8336-42. doi: 10.1021/jo9017155. PMID: 19778055 4:Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells. Bagley MC, Davis T, Dix MC, Rokicki MJ, Kipling D.Bioorg Med Chem Lett. 2007 Sep 15;17(18):5107-10. Epub 2007 Jul 13. PMID: 17659871 5:VX-745. Vertex Pharmaceuticals. Haddad JJ.Curr Opin Investig Drugs. 2001 Aug;2(8):1070-6. Review. PMID: 11892915