MW-150 dihydrochloride dihydrate (MW01-18-150SRM dihydrochloride dihydrate) is a selective, CNS-penetrant, and orally active p38α MAPK inhibitor with a Ki of 101 nM. It inhibits the endogenous p38α MAPK's ability to phosphorylate the endogenous substrate MK2 in activated glia [1].

p38α:101 nM (Ki)

MW-150 dihydrochloride dihydrate concentration-dependently inhibits the ability of the endogenous p38αMAPK to phosphorylate an endogenous substrate MK2 in activated glia [1]. MW-150 dihydrochloride dihydrate blocks in a concentration-dependent manner the increased IL-1β production by activated glia. The IC 50 values are 332 nM and 936 nM for MK2 and IL-1β, respectively [1].

MW-150 dihydrochloride dihydrate administered orally at a dosage of 2.5 mg/kg daily for 3 to 4 months enhances cognitive abilities in APP/PS1 transgenic mice, as evidenced by improved performance in the radial arm water maze (RAWM) and contextual fear conditioning tests. Similarly, when given intraperitoneally (i.p.) at the same dosage for 14 days, this treatment normalizes RAWM behavior in APP NLh/NLh × PS P264L/P264L knock-in mice, which do not overexpress the amyloid precursor protein, making their performance comparable to that of wild-type (WT) mice.