MW-150 hydrochloride (MW01-18-150SRM hydrochloride) is a potent and selective inhibitor of p38α MAPK with a Ki value of 101 nM. It exhibits excellent CNS penetration and oral bioavailability, and effectively suppresses the phosphorylation of MK2, a substrate of endogenous p38α MAPK, in activated glial cells.

p38α:101 nM (Ki)

MW-150 hydrochloride (MW01-18-150SRM hydrochloride) efficiently inhibits p38αMAPK phosphorylation of MK2 in activated glia and blocks the increased production of IL-1β in a concentration-dependent manner. The IC50 values for inhibiting MK2 and IL-1β are 332 nM and 936 nM, respectively[1].

Administering MW-150 hydrochloride (MW01-18-150SRM hydrochloride) at a dosage of 2.5 mg/kg orally each day for 3-4 months significantly enhances cognitive performance in APP/PS1 transgenic (Tg) mice, as evidenced in radial arm water maze (RAWM) and contextual fear conditioning tests. Similarly, a 14-day intraperitoneal (i.p.) treatment of the same dosage in APP NLh/NLh × PS P264L/P264L knock-in mice, which do not overexpress the amyloid precursor protein, results in RAWM performance comparable to that of wild-type (WT) mice. These findings suggest that MW-150 hydrochloride can ameliorate cognitive deficits in mouse models of amyloid-beta overexpression.