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.
