ArticleBritish journal of pharmacology2020
Negative allosteric modulators of the human calcium-sensing receptor bind to overlapping and distinct sites within the 7-transmembrane domain.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- A novel chemoreactive calcilytic for the potential treatment of autosomal dominant hypocalcemia.Acta pharmaceutica Sinica. B · 2025Article
- A calcium-sensing receptor allelic series and underdiagnosis of genetically driven hypocalcemia.American journal of human genetics · 2025Article
- A calcium-sensing receptor dileucine motif directs internalization to spatially distinct endosomal signaling pathways.iScience · 2025Article
- Article
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- Symmetric activation and modulation of the human calcium-sensing receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor.Science advances · 2021Article
- Therapeutic Opportunities of Targeting Allosteric Binding Sites on the Calcium-Sensing Receptor.ACS pharmacology & translational science · 2021Review
- Structural Mechanism of Cooperative Regulation of Calcium-Sensing Receptor-Mediated Cellular Signaling.Current opinion in physiology · 2020Article
- The Effect of High-Fat Diet-Induced Obesity on the Expression of Nutrient Chemosensors in the Mouse Stomach and the Gastric Ghrelin Cell.Nutrients · 2020Article
- International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function.Pharmacological reviews · 2020Review
- Negative allosteric modulators of the human calcium-sensing receptor bind to overlapping and distinct sites within the 7-transmembrane domain.British journal of pharmacology · 2020Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeNegative allosteric modulators (NAMs) that target the calcium-sensing receptor (CaS receptor) were originally developed for the treatment of osteoporosis by stimulating the release of endogenous parathyroid hormone, but failed in human clinical trials. Several chemically and structurally distinct NAM scaffolds have been described, but it is not known how these different scaffolds interact with the CaS receptor to inhibit receptor signalling in response to agonists. EXPERIMENTAL APPROACH: In the present study, we used a mutagenesis approach combined with analytical pharmacology and computational modelling to probe the binding sites of four distinct NAM scaffolds. KEY
resultsAlthough all four scaffolds bind to the 7-transmembrane and/or extracellular or intracellular loops, they occupy distinct regions, as previously shown for positive allosteric modulators of the CaS receptor. Furthermore, different NAM scaffolds mediate negative allosteric modulation via distinct amino acid networks. CONCLUSION AND IMPLICATIONS: These findings aid our understanding of how different NAMs bind to and inhibit the CaS receptor. Elucidation of allosteric binding sites in the CaS receptor has implications for the discovery of novel allosteric modulators.
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