The parathyroid hormone receptor (PTH1R), a class B1 GPCR,327 is activated by parathyroid hormone and parathyroid hormone-related peptides and plays a central role in maintaining mineral ion homeostasis and skeletal metabolism.328–330 Recently, a highly selective PTH1R agonist, the orally active non-peptidic small molecule PCO371 (54) (Fig. 28), was identified and is currently undergoing phase 1 clinical trials to treat hypoparathyroidism.331,332 PCO371 consists of four chemical modules, from left to right: trifluoromethoxyphenyl, spiro-imidazolone, dimethylphenyl, and dimethylhydantoin.333. Here, PTH is linked to hypoparathyroidism.