Biological activity
VX-702 is a highly selective p38α MAPK inhibitor, 14-fold more potent against p38α than against p38β. Phase 2.
Description
VX-
702 is a third generation inhibitor of p38 mitogen-
activated protein (MAP) kinases, binding to both p38α and p38β (K
d = 3.7 and 17 nM, respectively) in an ATP-
competitive fashion. It inhibits IL-
6, IL-
1β, and TNF-
α production in LPS-
primed blood with IC
50 values of 59, 122, and 99 ng/ml, respectively. VX-
702, at 1 μM, inhibits activation of p38 in platelets by thrombin, U-
46619 , or collagen but does not block platelet aggregation in response to collagen. Although orally active, VX-
702 provides only transient suppression of biomarkers of inflammation in ongoing rheumatoid arthritis.
Uses
VX-702 is a third generation inhibitor of p38 mitogen-activated protein (MAP) kinases, binding to both p38α and p38β (Kd = 3.7 and 17 nM, respectively) in an ATP-competitive fashion. It inhibits IL-6, IL-1β, and TNF-α production in LPS-primed blood with IC50 values of 59, 122, and 99 ng/ml, respectively. VX-702, at 1 μM, inhibits activation of p38 in platelets by thrombin, U-46619 , or collagen but does not block platelet aggregation in response to collagen. Although orally active, VX-702 provides only transient suppression of biomarkers of inflammation in ongoing rheumatoid arthritis.[Cayman Chemical]
Uses
VX-702 is a p38 mitogen-activated protein kinase (MAPK) inhibitor. VX-702 had no effect on platelet aggregation induced by any of the p38 MAPK agonists. VX-702 has potential use in the treatment of inflammation, rheumatoid arthritis and cardiovascular diseases.
Definition
ChEBI: 6-(N-carbamoyl-2,6-difluoroanilino)-2-(2,4-difluorophenyl)-3-pyridinecarboxamide is a phenylpyridine.
References
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
