1933460-19-5

Mitiperstat (AZD4831) is an effective oral inhibitor of myeloperoxidase (MPO). Mitiperstat inhibits MPO and thyroid peroxidase (TPO) with IC50s of 1.5 nM and 0.69 μM. Mitiperstat exhibits a weak inhibitory activity against CYP3A4 with an IC50 of 6 μM. Mitiperstat can reduce inflammation and improve microvascular function, and it can be used in studies related to heart failure, preserved or mildly reduced ejection fraction, non-alcoholic fatty liver disease, and chronic obstructive pulmonary disease[1][2][3][4].

[1] Joanna Parkinson， et al. The myeloperoxidase inhibitor mitiperstat (AZD4831) does not prolong the QT interval at expected therapeutic doses. Pharmacol Res Perspect. 2024 Apr;12(2):e1184. DOI:10.1002/prp2.1184
[2] Lars H Lund, et al. Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction. Eur J Heart Fail. 2023 Sep;25(9):1696-1707. DOI:10.1002/ejhf.2977
[3] Carolyn S P Lam, et al. Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results. J Card Fail. 2024 Jan;30(1):104-110. DOI:10.1016/j.cardfail.2023.04.003
[4] Inghardt T, et al., Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction. J Med Chem. 2022 Sep 8;65(17):11485-11496. DOI:10.1021/acs.jmedchem.1c02141