Target Engagement Analysis and Link to Pharmacodynamic Endpoint for a Novel Class of CNS-penetrant and Efficacious p38α MAPK Inhibitors

We report here more detailed analyses of MW181 target engagement and specific linkage to the downstream increase in glia proinflammatory cytokine production. In vivo validation included demonstration that oral administration of MW181 suppresses lipopolysaccharide-induced increases in mouse brain IL-1β, TNFα, IL-6, IL-10, and CXCL1 but not in a drug-resistant p38α MAPK mutant mouse.
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research