2020 Volume 30 Issue 2 Pages 78-83
Cinacalcet hydrochloride is well-used for the treatment of secondary hyperparathyroidism as a CaSR agonist in dialysis patients. However, it is also known that cinacalcet has several issues such as adverse effects on the gastrointestinal tract (e.g., nausea and vomiting) and drug-drug interactions from strong CYP2D6 inhibition. We started the drug discovery efforts targeting CaSR agonists without the defects of cinacalcet, and it leaded the discovery of evocalcet. It shows excellent BA and does not inhibit CYPs such as 2D6. Evocalcet was approved for marketing as Orkedia® that contributes to the achievement of management targets for patients with secondary hyperparathyroidism by taking it once a day and reduces their adverse effects on upper gastrointestinal tracts. This research is an extraordinary drug discovery program where PAM (Positive Allosteric Modulator) of GPCR was succeeded to reach the market.
