Design, Synthesis, and Bioevaluation of Novel MyD88 Inhibitor c17 against Acute Lung Injury Derived from the Virtual Screen.

Myeloid differentiation primary response protein 88 (MyD88) is crucial to immune cascades mediated by Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 dysregulation has been linked to a wide variety of inflammatory diseases, making it a promising new target for anti-inflammatory and cancer therapy development. In this study, 46 compounds were designed and synthesized inspired by virtual screen hit. The anti-inflammatory activity of designed compounds was evaluated biologically, and was discovered to have a high binding affinity with MyD88. It inhibited the interaction of TLR4 and MyD88 and suppressed the NF-κB pathway. In addition, treatment led to the accumulation in the lungs of rats and attenuated LPS-induced ALI mice model. Furthermore, showed negligible toxicity . Together, these findings suggest that may serve as a potential therapeutical method for the treatment of ALI and as a lead structure for the continued development of MyD88 inhibitors.