Omapatrilat is an orally active dual inhibitor of ACE (angiotensin-converting enzyme) and NEP (neprilysin), with Ki values of 0.64 and 0.45 nM, respectively, capable of suppressing induced hypotension in rats.

ACE:0.64 nM (ki), NEP:8 nM, NEP:0.45 nM (ki), ACE:5 nM

Omapatrilat exhibits high activity against NEP (Ki=0.45 nM), NEP2 (Ki=25 nM), and ACE (Ki=0.64 nM), demonstrates moderate activity against APP (Ki=250 nM), and shows low activity against ECE1 [1].

Omapatrilat significantly promoted the excretion of urinary sodium, ANP, and cGMP in cynomolgus monkey experiments. Within 10-24 hours after administration, Omapatrilat reduced MAP by approximately 40 mmHg from baseline levels. Oral administration of Omapatrilat at 100 μmol/kg once daily resulted in a 38 mmHg reduction in systolic pressure by the third day of dosing [2].
Long-term oral administration of Omapatrilat alleviated aortic leakage and atherosclerotic plaque formation while enhancing the non-endothelium-dependent vasodilatory response to ANP [3].
Omapatrilat markedly inhibited ACE activity in rat plasma and increased plasma renin activity in rats [4].