molecules of the month

Context. Tenapanor (Ardelyx) is an oral, first-in-class Na+/H+ exchanger isoform 3 (NHE3) inhibitor approved by the FDA for irritable bowel syndrome with constipation (IBS-C) in adults. NHE3 is expressed predominantly in the gut and kidney and its role as a key mediator of sodium and water homeostasis makes the protein an ideal target for multiple disease states such as hypertension, heart/kidney failure, diabetes mellitus, irritable bowel syndrome (IBS), constipation, and even hyperphosphatemia. However, this also presents a drug discovery challenge since systemic exposure could mean an undesired inhibition of renal NHE3. Therefore, critical to the development of tenapanor for IBS-C by Ardelyx scientists was the identification of an agent with potent Na+/H+ antiport activity in the gut that exhibited poor…