A novel selective NLRP3 inhibitor shows disease-modifying potential in animal models of Parkinson's disease.

Pathological activation of the Nod-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome signaling underlies many autoimmune and neuroinflammatory conditions. Here we report that, a rationally designed, novel, orally active, selective NLRP3 inflammasome inhibitor, Usnoflast (ZYIL1), showed potent inhibition of ATP, Nigericin and monosodium urate-mediated interleukin (IL)-1β release in THP-1 cells and human PBMC. In isolated microglia cells, the IC of ZYIL1 mediated inhibition of IL-1β was 43 nM.

Nonclinical Pharmacokinetic Evaluation of Desidustat: a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia.

Background And Objectives: Desidustat is a novel prolyl hydroxylase domain (PHD) inhibitor for the treatment of anemia. The objective of this study was to investigate the pharmacokinetics and drug-drug interaction properties of desidustat using in vitro and in vivo nonclinical models.

Methods: In vitro, Caco2 cell permeability, plasma protein binding, metabolism, cytochrome P450 (CYP) inhibition, and CYP induction were examined.