MLN-4760

MLN-4760 is a potent and selective human ACE2 inhibitor (IC ₅₀ , 0.44 nM), with excellent selectivity (>5000-fold) versus related enzymes human testicular ACE (IC ₅₀ , >100 μM) and bovine carboxypeptidase A (CPDA; IC ₅₀ , 27 μM). MLN-4760 effectively quenches cleavage of the 7-Mca-YVADAPK(Dnp) in rhACE2. MLN-4760 shows pIC ₅₀ at rhACE2 of 8.5±0.1 and at rhACE of 4.4±0.2. MLN-4760 also shows pIC ₅₀ at rhACE2 of 4.7±0.1, 6.9±0.1 and at ACE of 4.4±0.1, 6.2±0.1 in murine heart and mononuclear cells (MNCs), resepctively.

MLN-4760 (100 μM, intracerebroventricular infusion for five days) significantly worsens neurological function at 4 h and 3 d post-stroke without significantly increasing infarct volume.