MW-150

MW-150 is an inhibitor of p38α MAPK (K_i = 101 nM).¹ It is 6-, 10-, and 14-fold selective for p38α MAPK over the serine/threonine protein kinase NLK, p38β MAPK, and p38δ MAPK, respectively, and is also selective over the enzymatically normal mutant p38α MAPK^T106M. It inhibits p38α MAPK phosphorylation of the endogenous substrate MAPK-activated protein kinase 2 (MK2) in LPS-activated glia in a concentration-dependent manner and decreases the levels of IL-1β in the same cells. MW-150 (2.5 mg/kg per day, i.p.) reduces the number of errors made in the spatial reference memory version of the radial arm water maze in aged amyloid precursor protein/presenilin 1 (APP/PS1) knock-in mice as a model of Alzheimer’s disease.

1.Roy, S.M., Grum-Tokars, V.L., Schavocky, J.P., et al.Targeting human central nervous system protein kinases: An isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse modelsACS Chem. Neurosci.6(4)666-680(2015)