MPO-IN-1 is a potent, orally active, and irreversible indole-containing inhibitor of myeloperoxidase (MPO). MPO-IN-1 has IC50s 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[1].
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 | Vss (L/kg) | T1/2 (h) | AUCinf (nM•h) p.o. | Cmax (nM) p.o. | PPB (%) | F (%) |
| 1/10 mg/kg i.v./p.o. | 9.8 | 2.6 | 2486 | 502 | 99.6 | 61 |
| 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. |
[1]. Patnaik A, et al. Discovery of a novel indole pharmacophore for the irreversible inhibition of myeloperoxidase (MPO). Bioorg Med Chem. 2020;28(12):115548.