Myeloperoxidase (MPO) inhibitors: an updated patent review (2020 - present)

Myeloperoxidase (MPO), a key enzyme involved in neutrophil extracellular trap formation and other inflammatory processes, has emerged as an attractive therapeutic target for cardiovascular, central nervous system, respiratory, and autoimmune diseases. To date, four irreversible MPO inhibitors have entered clinical trials; however, none have reached the market, highlighting the challenges of MPO drug discovery. AREAS COVERED: This review provides an overview of MPO biology, its pathological roles in inflammatory diseases, and recent advances in MPO drug discovery. It then systematically summarizes patent literature published between 2020 and 2026, identified through Espacenet, Google Patents, and SciFinder, comprehensively covering the structural optimization and pharmacological characterization of emerging MPO inhibitors, including small molecules, peptides, and antibodies. EXPERT OPINION: Patent analysis indicates that MPO drug discovery remains heavily dependent on legacy thioxanthine/deazathioxanthine scaffolds. Current efforts are primarily focused on overcoming historical liabilities through improving target selectivity and pharmacokinetic properties. In parallel, non-thioxanthine chemotypes are emerging, although most still exhibit suboptimal potency and therefore require further optimization. The development of dual- or multi-target MPO inhibitors may represent a promising strategy for addressing complex inflammatory networks.