MW150 (2.5 mg/kg; oral daily for 3-4 months) improves the APP/PS1 transgenic (Tg) mice performance in radial arm water maze (RAWM) and contextual fear conditioning tests[1]. MW150 (2.5 mg/kg; given i.p.; daily for 14 days) treatment in APPNLh/NLh × PSP264L/P264L knock-in mouse (with no overexpression of the amyloid precursor protein) exhibits RAWM behavior indistinguishable from WT mice[1]. Animal Model: APP/PS1 transgenic (Tg) mouse (overexpresses amyloid-beta)[1] Dosage: 2.5 mg/kg Administration: Oral daily; 3-4 months (until cognitive impairment is present) Result: Improved the Tg mice performance in radial arm water maze (RAWM) and contextual fear conditioning tests.
In Vitro
MW150 inhibits in a concentration-dependent manner the ability of the endogenous p38αMAPK to phosphorylate an endogenous substrate MK2 in activated glia[1]. MW150 blocks in a concentration-dependent manner the increased IL-1β production by activated glia. The IC50 values are 332 nM and 936 nM for MK2 and IL-1β, respectively[1].
Kinase Assay
Cell Assay
Animal Administration
References
[1]. Roy SM, et al. Targeting human central nervous system protein kinases: An isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse models. ACS Chem Neurosci. 2015 Apr 15;6(4):666-80.
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