Evidence mapPaperPMID 41366530Full record

ArticleCommunications chemistry2025

Systematic metabolite screening identifies functional regulators of the adenosine A2A receptor.

Prashant Rao, Manoj Rathinaswamy, Michelle Chan, Andrea Guzmán Paredes, Chirag Patel, Bernd J Wranik, Jonathan Powell, Dan Eaton, Jared Rutter, Kevin G Hicks and 2 more

Abstract read
In one paragraph

Article in Communications chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Prashant Rao *Calico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, USA.
Manoj Rathinaswamy *Calico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, USA.
Michelle ChanCalico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, USA.ORCID http://orcid.org/0009-0007-8128-2167
Andrea Guzmán ParedesPeter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, 6124 Harry Hines Blvd, Dallas, TX, USA.
Chirag PatelCalico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, USA.
Bernd J WranikCalico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, USA.
Jonathan PowellCalico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, USA.
Dan EatonCalico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3933-0958
Jared RutterDepartment of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
Kevin G HicksDepartment of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, USA. kevin.hicks@health.utah.edu.ORCID http://orcid.org/0000-0001-5067-7608
Amirhossein MafiCalico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, USA. amafi@calicolabs.com.ORCID http://orcid.org/0000-0002-8366-6785
Qi HaoCalico Life Sciences LLC, 1170 Veterans Blvd, South San Francisco, CA, USA. qhao@calicolabs.com.ORCID http://orcid.org/0000-0001-6246-2153

Funding

Mechanisms of metabolite signalingR35GM131854 · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2025 to 2025
$424k
NIGMS NIH HHS R35 GM131854
6 · The paper itself

Abstract

The adenosine A2A receptor (A2AR) is a Class A G protein-coupled receptor (GPCR) that regulates inflammation, glucose metabolism, and energy homeostasis in metabolically active tissues. While the effects of small-molecule ligands and protein interactions with A2AR have been extensively studied, the regulatory influence of endogenous metabolites remains unexplored. To address this gap, we employed the Mass spectrometry Integrated with equilibrium Dialysis for the discovery of Allostery Systematically (MIDAS) platform to screen a library of human metabolites for interactions with A2AR. This approach identified 180 metabolites that interact with A2AR, including allosteric and orthosteric modulators. We characterized the mechanisms of three metabolites previously unreported to interact with A2AR: prostaglandin D2, an allosteric antagonist that fully inhibits receptor signaling, and two orthosteric agonists, S-adenosyl-L-homocysteine and 2'-deoxyadenosine, that fully activate A2AR. Overall, these findings highlight the potential of the MIDAS platform to uncover previously unrecognized metabolite-GPCR interactions for research and therapeutic applications.

Identifiers

PMID41366530
PMCPMC12800297

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.