VX-745

VX-745 is a potent inhibitor of p38α MAPK (IC50=10nM) with 20-fold selectivity over p38β and 1000-fold selectivity over closely related kinases, ERK1, MK2 and JNK1-3. p38α is a member of the mitogen-activated protein kinase (MAPK) family of serine/threonine protein kinases and is widely expressed in endothelial, immune or inflammatory cells and plays a central role in the regulation of proinflammatory cytokine production including TNF-α, IL-1β and IL-6. VX-745 is an anti-inflammatory agent that blocks IL-1β and TNF-α release in whole blood in vitro with IC50 values of 150 and 180nM, respectively. VX-745 showed anti-inflammatory efficacy in an animal model of rheumatoid arthritis and recently anti-neuroinflammatory potential in prevention of early-stage Alzheimers diseases (AD).