MPO-IN-1 is a powerful and orally bioavailable indole-containing inhibitor that acts irrevocably on myeloperoxidase (MPO). With IC50 values of 2.6 μM and 5.3 μM for MPO and thyroid peroxidase (TPO), respectively, MPO-IN-1 effectively inhibits both enzymes. Furthermore, it exhibits remarkable MPO inhibitory activity in an acute inflammation mouse model.

Plasma MPO assay:2.6 μM , Fluorescent MPO peroxidation assay:0.12 μM

MPO-IN-1 (compound 2) (5 and 90 mg/kg; p.o.; four hours post-Zymosan A administration) significantly reduces MPO activity in a mouse peritonitis model of acute inflammation[1]. Mouse pharmacokinetic parameter of MPO-IN-1[1]. Dose V ss (L/kg) T 1/2 (h) AUC inf (nM?h) p.o. C max (nM) p.o. PPB (%) 1/10 mg/kg i.v./p.o. 9.8 2.6 2486 502 99.6 Animal Model: Male C57BL/6J mice (mouse peritonitis model of acute inflammation)[1]Dosage: 5 and 90 mg/kg Administration: p.o. (four hours post-Zymosan A administration) Result: Resulted in a ~50% reduction in the MPO activity at 90 mg/kg.