molecules of the month


oral MPO covalent inhibitor

Ph. IIb/III candidate in HFpEF

previous literature and selectivity opt

J. Med. Chem.

AstraZeneca, Gothenburg, SE

AZD4831 chemical structure oral MPO covalent inhibitor - AstraZeneca, Gothenburg, SE
5 mins read

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…

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