ArticleNature2014
Structure of the human P2Y12 receptor in complex with an antithrombotic drug.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 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
182 citing papers in PubMed, 392 citations in OpenAlex.
- Comparative bioavailability of a novel fixed-dose combination of ticagrelor and acetylsalicylic acid.Clinical pharmacology in drug development · 2026Trial
- 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
- Optimal strategy of switching from clopidogrel to ticagrelor in Chinese acute coronary syndrome patients with complicated coronary artery disease: the switching from clopidogrel to ticagrelor (SHIFT-CACS) study.Chinese medical journal · 2019Trial
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- 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
- A novel dual-action drug TJ94 facilitated by lipid nanocrystal formulations targeting neuroprotection and antithrombosis in ischemic stroke.Materials today. Bio · 2026Article
- Discovery and Evaluation of Novel Calenduloside E Derivatives Targeting HSP90β in Ox-LDL-Induced HUVECs Injury.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Hyperglycemia impairs microglia responding to retinal vasculopathy via enhanced norepinephrine-ADRB2 signaling.Journal of neuroinflammation · 2025Article
- Association between clopidogrel use and improved survival in critically ill patients with acute kidney injury: insights from MIMIC-IV database.BMC nephrology · 2025Article
- Liposomal formulation ofRSC advances · 2025Article
- UDP-glucose and MRS2905 agonist-bound states of the purinergic P2YCommunications biology · 2025Article
- Article
- P2YACS pharmacology & translational science · 2025Article
- Exploration of Fluorinated Pyrazolidine-3,5-Diones for Positron Emission Tomography Imaging of the P2YChemMedChem · 2025Article
- Design, Synthesis and Preclinical Evaluation of a Brain-Permeable PET Tracer for P2Y12 Receptor Imaging in the Brain.Journal of medicinal chemistry · 2025Article
- 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
- Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics.Journal of advanced research · 2025Review
122 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
21 authors at 6 institutions in 2 countries.
Funding
Abstract
P2Y receptors (P2YRs), a family of purinergic G-protein-coupled receptors (GPCRs), are activated by extracellular nucleotides. There are a total of eight distinct functional P2YRs expressed in human, which are subdivided into P2Y1-like receptors and P2Y12-like receptors. Their ligands are generally charged molecules with relatively low bioavailability and stability in vivo, which limits our understanding of this receptor family. P2Y12R regulates platelet activation and thrombus formation, and several antithrombotic drugs targeting P2Y12R--including the prodrugs clopidogrel (Plavix) and prasugrel (Effient) that are metabolized and bind covalently, and the nucleoside analogue ticagrelor (Brilinta) that acts directly on the receptor--have been approved for the prevention of stroke and myocardial infarction. However, limitations of these drugs (for example, a very long half-life of clopidogrel action and a characteristic adverse effect profile of ticagrelor) suggest that there is an unfulfilled medical need for developing a new generation of P2Y12R inhibitors. Here we report the 2.6 Å resolution crystal structure of human P2Y12R in complex with a non-nucleotide reversible antagonist, AZD1283. The structure reveals a distinct straight conformation of helix V, which sets P2Y12R apart from all other known class A GPCR structures. With AZD1283 bound, the highly conserved disulphide bridge in GPCRs between helix III and extracellular loop 2 is not observed and appears to be dynamic. Along with the details of the AZD1283-binding site, analysis of the extracellular interface reveals an adjacent ligand-binding region and suggests that both pockets could be required for dinucleotide binding. The structure provides essential insights for the development of improved P2Y12R ligands and allosteric modulators as drug candidates.
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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.