AVE-0657

AVE-0657 is an orally absorbable small molecule inhibitor of sodium/hydrogen exchanger 3 (NHE3), primarily developed by Sanofi (Sanofi-aventis). It was designed to selectively inhibit NHE3 in the apical membranes of the proximal tubules in the kidney, thereby reducing sodium reabsorption and potentially lowering blood pressure. The drug reached phase 2 clinical trials for indications including Cheyne-Stokes respiration, heart failure, obstructive sleep apnea hypopnea syndrome, and sleep apnea syndromes but development was discontinued. Preclinical studies demonstrated that AVE-0657 attenuates angiotensin II-induced hypertension by improving pressure-natriuresis response through selective inhibition of renal NHE3[1][2][5][6].