Abstract
The calcium sensing receptor (CaR) is a G protein-coupled receptor (GPCR) that plays a fundamental role in serum calcium homeostasis. The CaR is expressed on the chief cells of the parathyroid gland and is responsible for controlling the secretion of parathyroid hormone (PTH). PTH acts on several organs including the bone, kidney, and intestine to tightly regulate the concentration of serum calcium. Substances other than calcium that activate the CaR are referred to as calcimimetics. Calcimimetics that bind to the CaR as agonists are referred to as type I. Type II calcimimetics bind to a site that is distinct from the physiological ligand and function as positive allosteric modulators of the CaR. Type II calcimimetics amplify the sensitivity of the CaR to serum calcium and are thus able to lower the concentration of serum PTH. Calcimimetics are being pursued as therapeutics for the treatment of disorders that are characterized by elevated levels of PTH such as primary and secondary hyperparathyroidism (primary HPT and secondary HPT). In this review, we provide an overview of key results in the discovery of cinacalcet HCl (Sensipar® in the US, Mimpara® in Europe). In addition, other recently disclosed type II calcimimetics are discussed.
Keywords: Calcium sensing receptor, calcimimetics, cinacalcet, hyperparathyroidism, Mimpara®, parathyroid hormone, R-568, Sensipar®
Current Medicinal Chemistry
Title: Calcium Sensing Receptor Activators: Calcimimetics
Volume: 14 Issue: 28
Author(s): Paul E. Harrington and Christopher Fotsch
Affiliation:
Keywords: Calcium sensing receptor, calcimimetics, cinacalcet, hyperparathyroidism, Mimpara®, parathyroid hormone, R-568, Sensipar®
Abstract: The calcium sensing receptor (CaR) is a G protein-coupled receptor (GPCR) that plays a fundamental role in serum calcium homeostasis. The CaR is expressed on the chief cells of the parathyroid gland and is responsible for controlling the secretion of parathyroid hormone (PTH). PTH acts on several organs including the bone, kidney, and intestine to tightly regulate the concentration of serum calcium. Substances other than calcium that activate the CaR are referred to as calcimimetics. Calcimimetics that bind to the CaR as agonists are referred to as type I. Type II calcimimetics bind to a site that is distinct from the physiological ligand and function as positive allosteric modulators of the CaR. Type II calcimimetics amplify the sensitivity of the CaR to serum calcium and are thus able to lower the concentration of serum PTH. Calcimimetics are being pursued as therapeutics for the treatment of disorders that are characterized by elevated levels of PTH such as primary and secondary hyperparathyroidism (primary HPT and secondary HPT). In this review, we provide an overview of key results in the discovery of cinacalcet HCl (Sensipar® in the US, Mimpara® in Europe). In addition, other recently disclosed type II calcimimetics are discussed.
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Cite this article as:
Harrington E. Paul and Fotsch Christopher, Calcium Sensing Receptor Activators: Calcimimetics, Current Medicinal Chemistry 2007; 14 (28) . https://dx.doi.org/10.2174/092986707782794096
DOI https://dx.doi.org/10.2174/092986707782794096 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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