Evidence mapPaperPMID 42313639Full record

ReviewJournal of medicinal chemistry2026

Discovery of Small Molecule Ligands Targeting Orphan G Protein-Coupled Receptors GPR3, GPR6, and GPR12.

Xiaochen Tian, Saghir Ali, Jones A Addiah-Nickson, Haiying Chen, John A Allen, Jia Zhou

Abstract readReview
In one paragraph

Review in Journal of medicinal chemistry, 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

6 authors.

Xiaochen TianChemical Biology Program, Department of Pharmacology and Toxicology, and Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555, United States.
Saghir AliChemical Biology Program, Department of Pharmacology and Toxicology, and Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555, United States.ORCID 0000-0002-7400-5512
Jones A Addiah-NicksonChemical Biology Program, Department of Pharmacology and Toxicology, and Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555, United States.ORCID 0009-0004-8939-0531
Haiying ChenChemical Biology Program, Department of Pharmacology and Toxicology, and Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555, United States.ORCID 0000-0003-2841-5518
John A AllenChemical Biology Program, Department of Pharmacology and Toxicology, and Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555, United States.ORCID 0000-0002-6038-6633
Jia ZhouChemical Biology Program, Department of Pharmacology and Toxicology, and Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555, United States.ORCID 0000-0002-2811-1090

Funding

Discovery of GPR52 ligand probes for cocaine use disorderR01DA060228 · UNIVERSITY OF TEXAS MED BR GALVESTON · 2025 to 2025
$795k
GPR6: A Circuit-Level Druggable Target in Cocaine Use DisorderR21DA063306 · UNIVERSITY OF TEXAS MED BR GALVESTON · 2025 to 2025
$440k
NIDA NIH HHS R01 DA060228NIDA NIH HHS R21 DA063306
6 · The paper itself

Abstract

GPR3, GPR6, and GPR12 form a subfamily of Class A orphan G protein-coupled receptors (oGPCRs), for which endogenous ligands have not been identified. Despite their high sequence similarity, each receptor exhibits unique expression profiles in human tissues. Their physiological roles and therapeutic potential are gradually being understood, indicating their critical involvement in various diseases, including central nervous system (CNS) disorders, metabolic diseases, and cancer. Notably, the GPR6 inverse agonist CVN424 is currently in Phase III clinical trials for the treatment of Parkinson's disease (PD). The recent determination of high-resolution structures of GPR3, GPR6, and GPR12 has significantly enhanced their attractiveness as emerging therapeutic targets for drug discovery. Herein, we summarize the current understanding of the structural and functional characteristics of GPR3, GPR6, and GPR12. We further highlight recent progress in relevant ligand discovery and discuss the key challenges and opportunities in developing potent and selective modulators targeting these orphan receptors.

Indexed as

Drug DiscoveryReceptors, G-Protein-CoupledSmall Molecule LibrariesAnimalsHumansLigandsGPR3 protein, humanGPR6 protein, humanLigandsReceptors, G-Protein-CoupledSmall Molecule Libraries

Identifiers

PMID42313639
PMCPMC13472643

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.