Discovery of a Novel MyD88 Inhibitor M20 and Its Protection Against Sepsis-Mediated Acute Lung Injury.

ABSTRACT: Myeloid differentiation factor 88 (MyD88) is a hub protein in the Toll-like receptor signaling pathway, which acts as a master switch for numerous inflammatory diseases, including acute lung injury (ALI). Although this protein is considered as a crucial therapeutic target, there are currently no clinically approved MyD88-targeting drugs. Based on previous literature, here we report the discovery via computer-aided drug design (CADD) of a small molecule, M20, which functions as a novel MyD88 inhibitor to efficiently relieve lipopolysaccharide-induced inflammation both in vitro and in vivo. Computational chemistry, surface plasmon resonance detection (SPR) and biological experiments demonstrated that M20 forms an important interaction with the MyD88-Toll/interleukin-1 receptor

SUBMITTER: Song J 

PROVIDER: S-EPMC8666603 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature