ArticleNature2014
Agonist-bound structure of the human P2Y12 receptor.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
142 citing papers in PubMed, 343 citations in OpenAlex.
- Prasugrel Intermediate Metabolite Modulates Platelet Inhibition by Negatively Interfering With an Active Metabolite: An Ex Vivo, In Vitro, and In Silico Study.Arteriosclerosis, thrombosis, and vascular biology · 2025Trial
- Advances in nucleotide-based P2Y₁ antagonism: implications for cardiovascular therapeutics.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Investigation of reported small molecule P2Y6 receptor antagonists.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Extending MMPBSA for membrane proteins: Addressing P2YBiophysical journal · 2026Article
- An Improved Cysteine-Based Labeling Strategy for GPCR Structural Dynamics Studies.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Phytochemical Profiling, Antiplatelet Potential, and Cytotoxic Assessment of Thymelaea tartonraira Aerial Part Essential Oil: In Vitro and In Silico Studies.Chemistry & biodiversity · 2026Article
- In vitro and ex vivo Pharmacological Profile of HY-022619, a Novel Intravenous P2YPharmaceutical research · 2026Article
- Computational discovery and repurposing of chloramphenicol succinate as a potent P2YJournal of advanced research · 2026Article
- Article
- Bisphenols-enhanced platelet aggregation via TP, P2YFrontiers in pharmacology · 2026Article
- The Allosteric Mechanism of G-Protein-Coupled Receptors is Induced Fit, Not Conformational Selection.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Article
- Identification of salvianolic acid A as an ADP receptor-selective and Gq/IPChinese medicine · 2025Article
- Article
- P2YACS pharmacology & translational science · 2025Article
- Article
- Role and recent progress of P2Y12 receptor in cancer development.Purinergic signalling · 2025Review
- Structural insight into the self-activation and G-protein coupling of P2Y2 receptor.Cell discovery · 2025Article
- Drug-like Antagonists of P2Y Receptor Subtypes: An Update.Journal of medicinal chemistry · 2025Review
- E. B. Hershberg Award: Taming Inflammation by Tuning Purinergic Signaling.Accounts of chemical research · 2025Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
The P2Y12 receptor (P2Y12R), one of eight members of the P2YR family expressed in humans, is one of the most prominent clinical drug targets for inhibition of platelet aggregation. Although mutagenesis and modelling studies of the P2Y12R provided useful insights into ligand binding, the agonist and antagonist recognition and function at the P2Y12R remain poorly understood at the molecular level. Here we report the structures of the human P2Y12R in complex with the full agonist 2-methylthio-adenosine-5'-diphosphate (2MeSADP, a close analogue of endogenous agonist ADP) at 2.5 Å resolution, and the corresponding ATP derivative 2-methylthio-adenosine-5'-triphosphate (2MeSATP) at 3.1 Å resolution. These structures, together with the structure of the P2Y12R with antagonist ethyl 6-(4-((benzylsulfonyl)carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283), reveal striking conformational changes between nucleotide and non-nucleotide ligand complexes in the extracellular regions. Further analysis of these changes provides insight into a distinct ligand binding landscape in the δ-group of class A G-protein-coupled receptors (GPCRs). Agonist and non-nucleotide antagonist adopt different orientations in the P2Y12R, with only partially overlapped binding pockets. The agonist-bound P2Y12R structure answers long-standing questions surrounding P2Y12R-agonist recognition, and reveals interactions with several residues that had not been reported to be involved in agonist binding. As a first example, to our knowledge, of a GPCR in which agonist access to the binding pocket requires large-scale rearrangements in the highly malleable extracellular region, the structural and docking studies will therefore provide invaluable insight into the pharmacology and mechanisms of action of agonists and different classes of antagonists for the P2Y12R and potentially for other closely related P2YRs.
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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.