Evidence map›Paper›PMID 27136943›Full record

ArticleMolecular pharmacology2016

Structure-Activity Analysis of Biased Agonism at the Human Adenosine A3 Receptor.

Jo-Anne Baltos, Silvia Paoletta, Anh T N Nguyen, Karen J Gregory, Dilip K Tosh, Arthur Christopoulos, Kenneth A Jacobson, Lauren T May

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
6.7field-weighted citation impact, top 3% of its field
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

20 citing papers in PubMed, 43 citations in OpenAlex.

  1. Structure-based discovery of positive allosteric modulators of the AProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Assessment of biased agonism at the ABiochemical pharmacology · 2020
    Article
  8. Functional Expression of Adenosine AInternational journal of molecular sciences · 2020
    Article
  9. Article
  10. Article
  11. Review
  12. Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity.The international journal of neuropsychopharmacology · 2018
    Review
  13. AMedicinal research reviews · 2018
    Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Human Adenosine AFrontiers in pharmacology · 2017
    Review
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 at 2 institutions in 2 countries.

Jo-Anne BaltosDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (J.-A.B., A.T.N.N., K.J.G., A.C., L.T.M); and Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland (S.P., D.K.T., K.A.J).
Silvia PaolettaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (J.-A.B., A.T.N.N., K.J.G., A.C., L.T.M); and Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland (S.P., D.K.T., K.A.J).
Anh T N NguyenDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (J.-A.B., A.T.N.N., K.J.G., A.C., L.T.M); and Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland (S.P., D.K.T., K.A.J).
Karen J GregoryDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (J.-A.B., A.T.N.N., K.J.G., A.C., L.T.M); and Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland (S.P., D.K.T., K.A.J).
Dilip K ToshDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (J.-A.B., A.T.N.N., K.J.G., A.C., L.T.M); and Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland (S.P., D.K.T., K.A.J).
Arthur ChristopoulosDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (J.-A.B., A.T.N.N., K.J.G., A.C., L.T.M); and Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland (S.P., D.K.T., K.A.J).
Kenneth A JacobsonDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (J.-A.B., A.T.N.N., K.J.G., A.C., L.T.M); and Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland (S.P., D.K.T., K.A.J).
Lauren T MayDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (J.-A.B., A.T.N.N., K.J.G., A.C., L.T.M); and Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland (S.P., D.K.T., K.A.J) lauren.may@monash.edu.
National Institute of Diabetes and Digestive and Kidney Diseases · USMonash University · AU

Funding

Development Of Drugs Acting At Adenosine ReceptorsZIADK031117 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI JACOBSON, KENNETH ALAN · 2009 to 2025
$10.4M
Intramural NIH HHS ZIA DK031117
6 · The paper itself

Abstract

Biased agonism at G protein-coupled receptors (GPCRs) has significant implications for current drug discovery, but molecular determinants that govern ligand bias remain largely unknown. The adenosine A3 GPCR (A3AR) is a potential therapeutic target for various conditions, including cancer, inflammation, and ischemia, but for which biased agonism remains largely unexplored. We now report the generation of bias "fingerprints" for prototypical ribose containing A3AR agonists and rigidified (N)-methanocarba 5'-N-methyluronamide nucleoside derivatives with regard to their ability to mediate different signaling pathways. Relative to the reference prototypical agonist IB-MECA, (N)-methanocarba 5'-N-methyluronamide nucleoside derivatives with significant N(6) or C2 modifications, including elongated aryl-ethynyl groups, exhibited biased agonism. Significant positive correlation was observed between the C2 substituent length (in Å) and bias toward cell survival. Molecular modeling suggests that extended C2 substituents on (N)-methanocarba 5'-N-methyluronamide nucleosides promote a progressive outward shift of the A3AR transmembrane domain 2, which may contribute to the subset of A3AR conformations stabilized on biased agonist binding.

Indexed as

AdenosineAdenosine A3 Receptor AgonistsAnimalsCHO CellsCricetinaeCricetulusHumansLigandsMolecular Docking SimulationReceptor, Adenosine A3Signal TransductionStructure-Activity RelationshipAdenosineAdenosine A3 Receptor AgonistsLigandsN(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosineReceptor, Adenosine A3

Identifiers

PMID27136943
PMCPMC4931866
OpenAlexW2346730296

What OpenQuestion 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 OpenQuestion graph.