Evidence map›Paper›PMID 42146503›Full record

ArticlebioRxiv : the preprint server for biology2026

Pharmacological proximities in the GPCR family discovered using contact-informed amino-acid and binding pocket similarities.

Sean S So, Tony Ngo, Andrey V Ilatovskiy, Angela M Finch, R Peter Riek, Ruben Abagyan, Nicola J Smith, Irina Kufareva

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. 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

8 authors.

Sean S SoOrphan Receptor Laboratory, Department of Pharmacology, School of Biomedical Sciences, Faculty of Medicine & Health, UNSW Sydney, Sydney, NSW, Australia.ORCID 0000-0002-1996-2045
Tony NgoVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.ORCID 0000-0002-6779-2546
Andrey V IlatovskiySkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0001-5975-0445
Angela M FinchSchool of Biomedical Sciences, Faculty of Medicine & Health, UNSW Sydney, Sydney, NSW, Australia.ORCID 0000-0002-4598-6745
R Peter RiekVictor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
Ruben AbagyanSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Nicola J SmithOrphan Receptor Laboratory, Department of Pharmacology, School of Biomedical Sciences, Faculty of Medicine & Health, UNSW Sydney, Sydney, NSW, Australia.ORCID 0000-0002-7247-9562
Irina KufarevaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0001-9083-7039

Funding

The Cancer Cell Map Initiative v2.0U54CA274502 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$14.2M
It's a tug of war: structure, consequences, and inhibition of CXCR4 and ACKR3 responses to lymphocyte chemoattractant CXCL12R01AI161880 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M, KUFAREVA, IRINA · 2021 to 2025
$3.4M
The structural plasticity of chemokine and gp120 recognition by CCR5R01AI118985 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M, KUFAREVA, IRINA · 2015 to 2019
$2.7M
Signaling circuits that drive cell movement and ligand scavenging by chemokine receptor CCR2R01GM136202 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M, KUFAREVA, IRINA · 2020 to 2023
$1.9M
Spatiotemporally resolved architecture of G protein signaling downstream of CXCR4, the driver of lymphocyte migrationR21AI156662 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KUFAREVA, IRINA · 2021 to 2022
$434k
Computationally informed discovery of scavenging-sparing inhibitors of CC chemokine receptor 2R21AI149369 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KUFAREVA, IRINA · 2020 to 2021
$434k
NCI NIH HHS U54 CA274502NIAID NIH HHS R01 AI118985NIAID NIH HHS R01 AI161880NIAID NIH HHS R21 AI149369NIAID NIH HHS R21 AI156662NIGMS NIH HHS R01 GM136202
6 · The paper itself

Abstract

Understanding protein proximities in the theoretical ligand space is essential for developing therapeutics with desirable polypharmacology, predicting off-targets, and discovering surrogate ligands for poorly characterized proteins. This is especially important for G protein-coupled receptors (GPCRs) - a major class of drug targets, many of which still lack known ligands. Circumventing this limitation, we present GPCR-CoINPocket v2, a contact-informed metric for detecting GPCR pharmacological similarities from amino-acid sequences alone. We first establish a "gold standard" of pharmacological relatedness using ChEMBL-derived ligand sets. We then replace traditional evolutionary amino acid similarity matrices with a chemically-informed matrix derived from protein:ligand interaction patterns across 3,306 structures, significantly improving early detection of shared pharmacology between distantly homologous receptors. An additional unconstrained, contact-informed matrix further enhances predictive performance. Pilot application of the method revealed previously unrecognized similarities between the β

Identifiers

PMID42146503
PMCPMC13174628

What OpenQuestion holds

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LicenceCC BY-NC
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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.