Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor.
Agarwal S,Pethani JP,Shah HA,Vyas V,Sasane S,Bhavsar H,Bandyopadhyay D,Giri P,Viswanathan K,Jain MR,Sharma R
NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases, including COVID-19. In this study, rationally designed alkenyl sulfonylurea derivatives were identified as novel, potent and orally bioavailable NLRP3 inhibitors. Compound 7 was found to be potent (IL-1β IC = 35 nM; IL-18 IC = 33 nM) and selective NLRP3 inflammasome inhibitor with excellent pharmacokinetic profile having oral bioavailability of 99% in mice.