PTH/PTHrP-R Inhibitors

PTH/PTHrP-R inhibitors target the parathyroid hormone (PTH) and parathyroid hormone-related protein receptor (PTHrP-R), which are key components in the regulation of calcium homeostasis in the body. PTH is a peptide hormone secreted by the parathyroid glands and plays a vital role in regulating the concentration of calcium in the blood. When calcium levels are low, PTH is released, which acts on various tissues, including the kidneys, intestines, and bones, to increase the blood calcium levels. PTHrP, on the other hand, is structurally and functionally related to PTH and can bind to the same receptor. While PTH is predominantly involved in calcium homeostasis, PTHrP has diverse roles, including acting as an autocrine, paracrine, and endocrine factor in various tissues, and its functions extend beyond calcium regulation.

The PTH/PTHrP receptor (PTH/PTHrP-R) is a G-protein-coupled receptor (GPCR) that gets activated upon binding with PTH or PTHrP. This receptor is primarily expressed in bones and kidneys. In the bone, activation of the receptor results in the release of calcium into the bloodstream, while in the kidneys, it leads to increased reabsorption of calcium. Inhibitors of the PTH/PTHrP-R function by blocking the interaction of PTH and PTHrP with their shared receptor. This blockade can modulate the signaling pathways downstream of the receptor activation, thus influencing the physiological effects associated with PTH and PTHrP. Given the pivotal role of the PTH/PTHrP-R in maintaining calcium balance, understanding these inhibitors and their mechanisms of action can provide insights into the intricate processes governing calcium homeostasis in the body.