Structure based drug design of new allosteric inhibitors targeting NLRP3 inflammasome

Abstract

Inflammasomes are vital defenders of the innate immune system, they have been substantially studied and classified. NLRP3 inflammasome activation is linked to various diseases like type2 diabetes and arthritis, more potent selective inhibitors and diagnostics are needed to eliminate the pathological effects of the NLRP3 inflammasome overactivation. Which facilitated the research focus on improving the understanding of the NLRP3 inflammasome structure and the mechanism of activation to develop new effective NLRP3 binding molecules. In this study, we used computational chemistry methods to develop new selective inhibitors for NLRP3 inflammasome based on a previously found molecule MCC90 that is an allosteric NLRP3 inhibitor. We also designed new BODIPY molecules that can be used for diagnostics/imaging besides the lead inhibitors for NLRP3 inflammasome. We aimed to improve the pharmacokinetic properties of the molecules and analyze the structure activity relationship of each complex.