Synthetic heterocyclic scaffolds relevant to human 15-lipoxygenase-2 (h15-LOX-2) inhibition: Scaffold diversity, structure-activity relationships, selectivity challenges, and future directions. (PubMed, Eur J Med Chem) - Jun 13, 2026 - "Critically, while zileuton remains the sole clinically approved lipoxygenase-targeting drug, it is clinically used as a 5-LOX inhibitor for asthma and is not an h15-LOX-2-targeted therapy...Outstanding challenges including the scarcity of ex vivo validated compounds, species-specific translational barriers arising from divergent murine ortholog function, and the absence of wild-type inhibitor co-crystal structures are critically evaluated. Future directions encompassing covalent inhibitor strategies, PROTAC-based targeted degradation, and selective modulation of the pro-ferroptotic h15-LOX-2/PEBP1 complex are discussed as promising avenues to fully realize the therapeutic potential of this target."
Journal • Review • Asthma • Atherosclerosis • Cardiovascular • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • ALOX15B • PEBP1
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