Novel Non-catalytic Substrate-selective p38a-specific MAPK Inhibitors with Endothelial-Stabilizing and Anti-inflammatory Activity

We developed a novel substrate-selective inhibitor of p38 MAPK, UM101, and compared its effects on TNF-induced gene expression by human lung microvascular endothelial cells (HMVECLs) with the prototypical p38 catalytic inhibitor, SB203580 Overall design: HMVECLs were pretreated with DMSO (vehicle), UM101, or SB203580, then stimulated with TNF for 3h. Total RNA from treated cells and untreated control HMVECLs was isolated, poly(A) mRNA enriched and sequenced using the Illumina HiSeq platform.