Brain Penetrant NLRP3 Inhibitors: The Discovery of a Panacea?

Abstract

The NLRP3 inflammasome has attracted much interest as a drug target; however, many of the first wave of inhibitors were derived from a single aryl sulfonylurea starting point. The physicochemical properties of this molecule and most derivatives are not amenable to high brain penetration, thus limiting their potential effectiveness against disease targets where this is required. The disclosure of a novel pyridazine phenol scaffold facilitated a second wave of research toward brain-penetrant molecules, which may enable the discovery of novel treatments for Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and cardiometabolic diseases.