Evidence map›Paper›PMID 25837834›Full record

ReviewMolecular pharmacology2015

Nucleotides Acting at P2Y Receptors: Connecting Structure and Function.

Kenneth A Jacobson, Silvia Paoletta, Vsevolod Katritch, Beili Wu, Zhan-Guo Gao, Qiang Zhao, Raymond C Stevens, Evgeny Kiselev

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

54 citing papers in PubMed.

  1. 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 · 2026
    Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Purinergic P2X7R as a potential target for pancreatic cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Review
  10. Review
  11. Review
  12. Physiologic roles of P2 receptors in leukocytes.Journal of leukocyte biology · 2022
    Review
  13. Amplified CaInternational journal of cancer · 2022
    Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Kenneth A JacobsonMolecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (K.A.J., S.P., Z.-G.G., E.K.); The Bridge Institute, Dana and David Dornsife School of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California (V.K., R.C.S.); and Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (B.W., Q.Z.) kajacobs@helix.nih.gov.ORCID http://orcid.org/0000-0001-8104-1493
Silvia PaolettaMolecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (K.A.J., S.P., Z.-G.G., E.K.); The Bridge Institute, Dana and David Dornsife School of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California (V.K., R.C.S.); and Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (B.W., Q.Z.).
Vsevolod KatritchMolecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (K.A.J., S.P., Z.-G.G., E.K.); The Bridge Institute, Dana and David Dornsife School of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California (V.K., R.C.S.); and Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (B.W., Q.Z.).
Beili WuMolecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (K.A.J., S.P., Z.-G.G., E.K.); The Bridge Institute, Dana and David Dornsife School of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California (V.K., R.C.S.); and Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (B.W., Q.Z.).
Zhan-Guo GaoMolecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (K.A.J., S.P., Z.-G.G., E.K.); The Bridge Institute, Dana and David Dornsife School of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California (V.K., R.C.S.); and Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (B.W., Q.Z.).
Qiang ZhaoMolecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (K.A.J., S.P., Z.-G.G., E.K.); The Bridge Institute, Dana and David Dornsife School of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California (V.K., R.C.S.); and Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (B.W., Q.Z.).
Raymond C StevensMolecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (K.A.J., S.P., Z.-G.G., E.K.); The Bridge Institute, Dana and David Dornsife School of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California (V.K., R.C.S.); and Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (B.W., Q.Z.).
Evgeny KiselevMolecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (K.A.J., S.P., Z.-G.G., E.K.); The Bridge Institute, Dana and David Dornsife School of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California (V.K., R.C.S.); and Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (B.W., Q.Z.).

Funding

Project 3U54GM094618 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI STEVENS, RAYMOND C · 2010 to 2014
$17.1M
Development Of P2Y Receptor LigandsZIADK031116 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI JACOBSON, KENNETH ALAN · 2009 to 2025
$8.9M
Computer Modeling of G Protein-Coupled ReceptorsZ01DK031126 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI JACOBSON, KENNETH ALAN · 2007 to 2008
$577k
Intramural NIH HHS Z01 DK031126Intramural NIH HHS ZIA DK031116NIDDK NIH HHS Z01-DK031126-08NIGMS NIH HHS U54 GM094618
6 · The paper itself

Abstract

Eight G protein-coupled P2Y receptor (P2YR) subtypes are important physiologic mediators. The human P2YRs are fully activated by ATP (P2Y2 and P2Y11), ADP (P2Y1, P2Y12, and P2Y13), UTP (P2Y2 and P2Y4), UDP (P2Y6 and P2Y14), and UDP glucose (P2Y14). Their structural elucidation is progressing rapidly. The X-ray structures of three ligand complexes of the Gi-coupled P2Y12R and two of the Gq-coupled P2Y1Rs were recently determined and will be especially useful in structure-based ligand design at two P2YR subfamilies. These high-resolution structures, which display unusual binding site features, complement mutagenesis studies for probing ligand recognition and activation. The structural requirements for nucleotide agonist recognition at P2YRs are relatively permissive with respect to the length of the phosphate moiety, but less so with respect to base recognition. Nucleotide-like antagonists and partial agonists are also known for P2Y1, P2Y2, P2Y4, and P2Y12Rs. Each P2YR subtype has the ability to be activated by structurally bifunctional agonists, such as dinucleotides, typically, dinucleoside triphosphates or tetraphosphates, and nucleoside polyphosphate sugars (e.g., UDP glucose) as well as the more conventional mononucleotide agonists. A range of dinucleoside polyphosphates, from triphosphates to higher homologs, occurs naturally. Earlier modeling predictions of the P2YRs were not very accurate, but recent findings have provided much detailed structural insight into this receptor family to aid in the rational design of new drugs.

Indexed as

Binding SitesHumansModels, MolecularNucleotidesProtein ConformationPurinergic P2Y Receptor AgonistsReceptors, Purinergic P2YStructure-Activity RelationshipNucleotidesPurinergic P2Y Receptor AgonistsReceptors, Purinergic P2Y

Identifiers

PMID25837834
PMCPMC4518082

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.