VX-702 | P38alpha MAP kinase inhibitor

VX-702 (745833-23-2) is a  potent and selective inhibitor of p38 MAP kinases, p38α MAPK and p38β (K_D = 3.7 and 17 nM respectively).¹ Inhibits IL-6, IL-1β and TNFα production in LPS-primed blood.¹ Inhibits p38 in platelets stimulated by thrombin, collagen, or thromboxane agonist U-46619 at 1 μM.² Provides only modest clinical efficacy in rheumatoid arthritis.^3,4 Delays platelet lesions and leads to better maintenance of stored platelets.⁵

References/Citations:

1) Goldstein et al. (2010), Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders; J. Med. Chem., 53 2345
2) Kuliopulos et al. (2004), Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation; Thromb. Haemostasis, 92 1387
3) Damianov et al. (2009), Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies; Arthrit. Rheumat., 60 1232
4) Ding et al. (2006), Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary syndrome; Curr. Opin. Investig. Drugs, 7 1020
5) Scripchenko et al. (2013), An inhibition of p38 mitogen activated protein kinase delays the platelet storage lesion; PLoS One, 8(8)e 70732