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

In conscious DOCA/salt hypertensive rats, intravenous administration of 300 μmol/kg SQ28603 significantly reduces 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 hours. SQ28603 also reduces the NEP activity in the kidney by 95% (1.28±0.08 vs. 18.35±0.61 μmol/min for SQ28603 and vehicle, respectively) and in the lungs by 77% (0.29±0.03 vs. 0.92±0.14 μmol/kg for SQ28603 and vehicle, respectively). Consequently, inhibition of NEP activity by SQ28603 significantly decreases MAP, increases plasma ANP concentrations, and enhances urinary excretion of cyclic GMP in conscious DOCA/salt hypertensive rats[1]. Additionally, in conscious female cynomolgus monkeys, SQ28603 (300 μmol/kg, approximately 80 mg/kg, i.v.) significantly increases sodium excretion from 4.9±2.3 to 14.3±2.1 μequiv./min and cyclic 3',5'-guanosine monophosphate excretion from 118±13 to 179±18 pmol/min[2].