Background:

PF-1355 is a selective 2-thiouracil mechanism-based MPO inhibitor, used for treatment of vasculitic diseases.

In a dose-responsive fashion, PF-1355 inhibits MPO activity in phorbol ester-stimulated human neutrophils as measured by taurine chlorination (EC50=1.47 μM) as well as lipopolysaccharide-treated human blood measuring residual MPO activity (EC50=2.03 μM)[1].

Oral administration of PF-1355 reduces plasma MPO activity, vascular edema, neutrophil recruitment, and elevates circulating cytokines. In a model of anti-glomerular basement membrane disease, formerly known as Goodpasture disease, albuminuria and chronic renal dysfunction are completely suppressed by PF-1355 treatment[1].

参考文献:
[1]. Zheng W, et al. PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis. J Pharmacol Exp Ther. 2015 May;353(2):288-98