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 STRATEGI AKTIF PASIF DALAM OPTIMALISASI PORTOFOLIO SAHAM INDEKS LQ-45 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 domain and thereby inhibits the protein dimerization.Taken together, this study found a MyD88 inhibitor, M20, with a novel skeleton, which provides a crucial understanding in the development and modification of MyD88 inhibitors.Meanwhile, the favorable bioactivity of the hit compound is also conducive to the treatment of acute lung injury or Factor analysis of ways to activate using the urban passenger motor transport other more inflammatory diseases.