A first-in-kind MAPK13 inhibitor corrects stem cell reprogramming and muco-obstructive lung disease.

ABSTRACT: The stress kinase MAPK13 (aka p38delta-MAPK) is an attractive entry point for therapeutic intervention because it regulates the structural remodeling that can develop after epithelial injury in the lung and likely other tissue sites. However, a selective, safe, and effective MAPK13 inhibitor is not yet available for experimental or clinical application. Here we identify a first-in-kind MAPK13 inhibitor using structure-based drug design combined with a screening funnel for cell safety and molecular specificity. This inhibitor (designated NuP-4A for intravenous or Nu4-B for inhaled delivery) down-regulates basal-epithelial stem cell reprogramming, structural remodeling, and pathophysiology equivalently to Mapk13 gene-knockout in mouse and mouse organoid models of muco-obstructive lung

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC11370402 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature