Selective myeloperoxidase (MPO) inhibitor (IC50
= 1.5 μ
M in LPS-stimulated human whole blood). Selective for MPO over a panel of 50 receptors, enzymes, ion channels and transporters, including thyroid peroxidase. Inhibits MPO activity in peritoneal lavage and plasma in a murine peritonitis model. Also reduces lung edema in a murine pulmonary immune complex vasculitis model. Orally bioavailable.
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PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis.
Zheng et al.
Discovery of 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A highly selective mechanism-based myeloperoxidase inhibitor for the treatment of cardiovascular diseases.
Ruggeri et al.