ArticleCell research2016
Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor.
Article in Cell research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 112 citations in OpenAlex.
- Exploring multiple drug actions of a CaNaunyn-Schmiedeberg's archives of pharmacology · 2026Review
- A novel chemoreactive calcilytic for the potential treatment of autosomal dominant hypocalcemia.Acta pharmaceutica Sinica. B · 2025Article
- Article
- Next-Generation Analogues of AC265347 as Positive Allosteric Modulators of the Calcium-Sensing Receptor: Pharmacological Investigation of Structural Modifications at the Stereogenic Centre.International journal of molecular sciences · 2025Article
- New calcimimetics for secondary hyperparathyroidism in CKD G5D: do they offer advantages?Journal of nephrology · 2025Review
- Measuring IP3 Generation in Real-Time Using a NanoBiT Luminescence Biosensor.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Measuring Calcium-Sensing Receptor Agonist-Driven Insertional Signaling (ADIS) and Trafficking by TIRF Microscopy.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Comparative Study of Allosteric GPCR Binding Sites and Their Ligandability Potential.Journal of chemical information and modeling · 2024Article
- Large library docking identifies positive allosteric modulators of the calcium-sensing receptor.Science (New York, N.Y.) · 2024Article
- Silicon-Rhodamine Functionalized Evocalcet Probes Potently and Selectively Label Calcium Sensing ReceptorsACS pharmacology & translational science · 2024Article
- Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges.Communications biology · 2024Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- Small vs. Large Library Docking for Positive Allosteric Modulators of the Calcium Sensing Receptor.bioRxiv : the preprint server for biology · 2024Article
- Structural insights into asymmetric activation of the calcium-sensing receptor-GCell research · 2024Article
- Article
- Identification and characterization of a novel CASR mutation causing familial hypocalciuric hypercalcemia.Frontiers in endocrinology · 2024Article
- Structure, function and drug discovery of GPCR signaling.Molecular biomedicine · 2023Review
- Abnormal changes of bone metabolism markers with age in children with cerebral palsy.Frontiers in pediatrics · 2023Article
- Allosteric modulation of G protein-coupled receptor signaling.Frontiers in endocrinology · 2023Review
- Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects CaJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Drugs that allosterically target the human calcium-sensing receptor (CaSR) have substantial therapeutic potential, but are currently limited. Given the absence of high-resolution structures of the CaSR, we combined mutagenesis with a novel analytical approach and molecular modeling to develop an "enriched" picture of structure-function requirements for interaction between Ca(2+)o and allosteric modulators within the CaSR's 7 transmembrane (7TM) domain. An extended cavity that accommodates multiple binding sites for structurally diverse ligands was identified. Phenylalkylamines bind to a site that overlaps with a putative Ca(2+)o-binding site and extends towards an extracellular vestibule. In contrast, the structurally and pharmacologically distinct AC-265347 binds deeper within the 7TM domains. Furthermore, distinct amino acid networks were found to mediate cooperativity by different modulators. These findings may facilitate the rational design of allosteric modulators with distinct and potentially pathway-biased pharmacological effects.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.