molecules of the month

Context. AZD4831 (AstraZeneca) is an oral covalent myeloperoxidase (MPO) inhibitor being developed for heart failure. Almost half of chronic heart disease patients suffer from heart failure with a preserved ejection fraction (HFpEF) and have an estimated five-year mortality rate of 75%. Improvement in vascular structure could help these patients, and targeting MPO is a potential way to achieve this. Extracellular MPO causes tissue damage by catalyzing the formation of reactive oxygen species. One of the first tool molecules, 4-aminobenzoic acid hydrazide, expanded our understanding of MPO’s mechanism of action and propelled the development of more potent inhibitors such as the thiopyrimidinone PF-06282999. The structure of AZD4831 was first disclosed at the fall ACS meeting in Chicago this year. Target. Myeloperoxidase…