MPO-IN-1 is a potent, orally active, and irreversible indole-containing inhibitor of myeloperoxidase ( MPO ). MPO-IN-1 has IC 50 s of 2.6 μM and 5.3 μM for MPO and thyroid peroxidase (TPO), respectively. MPO-IN-1 inhibits MPO activity in an acute mouse model of inflammation
In Vivo
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 . Mouse pharmacokinetic parameter of MPO-IN-1 . Dose V ss (L/kg) T 1/2 (h) AUC inf (nM•h) p.o. C max (nM) p.o. PPB (%) F (%) 1/10 mg/kg i.v./p.o. 9.8 2.6 2486 502 99.6 61 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male C57BL/6J mice (mouse peritonitis model of acute inflammation) 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.
Form:Solid
IC50& Target:2.6 μM (in plasma MPO assay),0.12 μM (in fluorescent MPO peroxidation assay)
