SQ28603 is a potent and selective neutral endopeptidase 3.4.24.11 (NEP) inhibitor.

In conscious deoxycorticosterone acetate (DOCA)/salt hypertensive rats, 300 μmol/kg, i.v., of SQ28603 significantly lowers mean arterial pressure (MAP) from 177±12 to 154±8 mm Hg and increases urinary cyclic guanosine monophosphate (GMP) excretion from 204±70 to 1,068±326 pmol/kg/min within 2 h. SQ28603 can also significantly reduce the NEP activity of the kidney by 95% (1.28±0.08 vs. 18.35±0.61μmol/min after SQ28603 and vehicle, respectively) and 77% of the lungs (0.29±0.03 vs. 0.92±0.14μmol/kg ) SQ28603 and vehicles). In conclusion, inhibition of NEP activity by SQ28603 significantly decreases MAP and increases plasma ANP concentrations and urinary excretion of cyclic GMP in conscious DOCA/salt hypertensive rats[1]. The potent neutral endopeptidase inhibitor SQ28603 significantly increases excretion of sodium from 4.9±2.3 to 14.3±2.1 muequiv./min and cyclic 3',5'-guanosine monophosphate from 118±13 to 179±18 pmol/min after intravenous administration of 300 μmol/kg (approximately 80 mg/kg) in conscious female cynomolgus monkeys[2].