PT2567

**PT2567** is a small-molecule inhibitor of hypoxia-inducible factor-2α (HIF-2α) that disrupts HIF-2α-ARNT heterodimerization, preventing DNA binding and transcriptional activity under hypoxic conditions. Developed by Peloton Therapeutics (a Merck & Co subsidiary), it is being investigated for pulmonary arterial hypertension (PAH) and pulmonary hypertension (PH), where aberrant HIF-2α stabilization drives vascular remodeling, inflammation, endothelial dysfunction, and right heart failure. Preclinical studies in Su5416/hypoxia and monocrotaline rodent models demonstrate that PT2567 reduces pulmonary hemodynamics, vascular remodeling, PH-associated gene expression in lung and heart tissues, arginase activity in PAH patient-derived endothelial cells, and monocyte recruitment, while restoring plasma nitrite and improving survival.[1][2][4][5][7][8]