Therapeutic Opportunities of Targeting Allosteric Binding Sites on the Calcium-Sensing Receptor
| Autor: | Jane E. Bourke, Jiayin Diao, Karen J. Gregory, Ben Capuano, Aaron DeBono, Katie Leach, Tracy M. Josephs |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
0303 health sciences Allosteric modulator Chemistry Allosteric regulation Endogeny 3. Good health Cell biology 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Pharmacology (medical) Binding site Calcium-sensing receptor Receptor Gene 030304 developmental biology G protein-coupled receptor |
| Zdroj: | ACS Pharmacol Transl Sci |
| ISSN: | 2575-9108 |
| DOI: | 10.1021/acsptsci.1c00046 |
| Popis: | [Image: see text] The CaSR is a class C G protein-coupled receptor (GPCR) that acts as a multimodal chemosensor to maintain diverse homeostatic functions. The CaSR is a clinical therapeutic target in hyperparathyroidism and has emerged as a putative target in several other diseases. These include hyper- and hypocalcaemia caused either by mutations in the CASR gene or in genes that regulate CaSR signaling and expression, and more recently in asthma. The development of CaSR-targeting drugs is complicated by the fact that the CaSR possesses many different binding sites for endogenous and exogenous agonists and allosteric modulators. Binding sites for endogenous and exogenous ligands are located throughout the large CaSR protein and are interconnected in ways that we do not yet fully understand. This review summarizes our current understanding of CaSR physiology, signaling, and structure and how the many different binding sites of the CaSR may be targeted to treat disease. |
| Databáze: | OpenAIRE |
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