Omapatrilat is a dual inhibitor of the metalloproteases ACE and NEP with K_i values of 0.64 and 0.45 nM, respectively. IC50 & Target: Ki: 0.45 nM (NEP), 0.64 nM (ACE)^[1]; IC50: 8 nM (NEP), 5 nM (ACE)^[2] In Vitro: Omapatrilat exhibits high potency for NEP, NEP2 and ACE, moderate strong activity against APP, but low activity against ECE1 (K_i=0.45, 25, 0.64, 250 nM) ^[1]. In vitro autoradiography using the specific NEP inhibitor radioligand 125I-RB104 and the specific ACE inhibitor radioligand 125I-MK351A show omapatril at (10 mg/kg) causes rapid and potent inhibition of renal NEP and ACE, respectively, for 24 h^[4]. In Vivo: Omapatrilat demonstrates excellent blood pressure lowering in a variety of animal models characterized by various levels of plasma renin activity and significantly potentiates urinary sodium, ANP, and cGMP excretion in a cynomolgus monkey assay. Omapatrilat decreases mean arterial pressure (MAP) approximately 40 mmHg below baseline from 10 to 24 h. Oral administration of omapatrilat at 100 μM/kg once daily results in a 38 mmHg decrease in systolic blood pressure at day three as compared to vehicle ^[2]. Omapatrilat is widely used in experimental protocols related to hypertension and heart failure. Chronic oral administration of omapatrilat reduces aortic leakiness and atheroma formation with enhanced endothelial independent vasorelaxation to ANP^[3]. Omapatrilat causes significant inhibition of plasma ACE and increased plasma renin activity in rats^[4].