DS-69910557

DS-69910557 is an orally available, potent, and selective small-molecule antagonist and inverse agonist of the parathyroid hormone 1 receptor (PTH1R). Originally discovered by Daiichi Sankyo through scaffold-hopping and optimization of a zwitterionic series of hPTHR1 antagonists, the compound is being investigated for its therapeutic potential in conditions of abnormal calcium homeostasis. Preclinical research led by Massachusetts General Hospital has demonstrated that DS-69910557 acts as a potent inverse agonist at constitutively active PTH1R mutants. This activity makes it a promising candidate for the treatment of Jansen's metaphyseal chondrodysplasia (JMC), an ultra-rare skeletal dysplasia characterized by severe growth-plate abnormalities, hypercalcemia, and hypophosphatemia. In humanized JMC mouse models, oral or subcutaneous administration of DS-69910557 successfully reduced elevated blood ionized calcium levels and improved growth-plate morphology.

Other names

4-[[1-[4-(2,9-dichloro-5,5-dimethyl-6-oxo-pyrido[2,3-d][1]benzazepin-7-yl)phenyl]-3-fluoro-azetidin-3-yl]methylamino]cyclohexanecarboxylic acidcompound 19ecompound19ecompound-19e