Competitive antagonists of the Parathyroid Hormone Receptor 1 identified through docking calculations to an inactive receptor conformation

Making use of the first published X-ray structure of the Parathyroid Hormone 1 Receptor, we employed small-molecule docking calculations in order to identify novel ligands. Besides directly using the experimental structure, we also generated several models through homology modeling or by reverting stabilizing mutations present in the experimental structure to wild-type. Our calculations yielded three ligands, two of which we further developed into two series of compounds through similarity searches and docking calculations. The set of ligands presented here enriches the landscape of Parathyroid Hormone 1 Receptor ligands, and introduces novel starting points for further development of compounds targeting disorders of calcium homeostasis and bone metabolism.