Targeting 15-PGDH for Drug Development Hung V. Le Biologics & Drug Targets, ProSci LLC, Rockaway, The United States ORCID https://orcid.org/0000-0002-6913-2373 (Hung Van Le) 02/10/2026 Abstract 15-Hydroxyprostaglandin dehydrogenase (15-PGDH), encoded by HPGD , is the principal enzyme responsible for the metabolic inactivation of prostaglandin E₂ (PGE₂), a lipid mediator with central roles in inflammation, tissue repair, stem cell function, and cancer biology. By constraining PGE₂ signaling, 15-PGDH functions as a dominant endogenous brake on regeneration. Across multiple tissues, aging and injury are associated with increased 15-PGDH activity, leading to impaired repair capacity. Recent preclinical studies demonstrate that pharmacologic inhibition of 15-PGDH restores physiologic PGE₂ signaling and robustly enhances regeneration in skeletal muscle, neuromuscular junctions, cartilage, hematopoietic stem cell niches, and the ...