Evidence map›Paper›PMID 40146900›Full record

ArticleJournal of medicinal chemistry2025

Development of Diphenyl-1,2,4-Oxadiazole Analogues as Allosteric Modulators of the RXFP3 Receptor: Evaluation of Importance of the N-Substituted-2-Pyrrolidone Moiety in RLX-33.

Dongliang Guan, Hetti Handi Chaminda Lakmal, Brooke N Bender, Md Toufiqur Rahman, Elaine A Gay, Daniel G Barrus, Alejandro M Mosera, Andrew T Kerr, Joyce Besheer, Chunyang Jin

Abstract read
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In one paragraph

Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

10 authors.

Dongliang GuanCenter for Drug Discovery, Research Triangle Institute, Research Triangle Park, North Carolina 27709, United States.ORCID 0000-0002-7814-1116
Hetti Handi Chaminda LakmalCenter for Drug Discovery, Research Triangle Institute, Research Triangle Park, North Carolina 27709, United States.
Brooke N BenderBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Md Toufiqur RahmanCenter for Drug Discovery, Research Triangle Institute, Research Triangle Park, North Carolina 27709, United States.ORCID 0000-0003-2752-6822
Elaine A GayCenter for Drug Discovery, Research Triangle Institute, Research Triangle Park, North Carolina 27709, United States.
Daniel G BarrusCenter for Drug Discovery, Research Triangle Institute, Research Triangle Park, North Carolina 27709, United States.
Alejandro M MoseraBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Andrew T KerrCenter for Biomolecular Science and Engineering, US Naval Research Laboratory, Washington, District of Columbia 20375, United States.
Joyce BesheerBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID 0000-0001-6187-8376
Chunyang JinCenter for Drug Discovery, Research Triangle Institute, Research Triangle Park, North Carolina 27709, United States.ORCID 0000-0001-6733-3094

Funding

Small molecule antagonist probes for the relaxin-3/RXFP3 systemR01AA028255 · NIAAA · RESEARCH TRIANGLE INSTITUTE · PI BESHEER, JOYCE, JIN, CHUNYANG · 2020 to 2022
$1.9M
NIAAA NIH HHS R01 AA028255
6 · The paper itself

Abstract

Relaxin-3/RXFP3 antagonism is a novel strategy for drug development to treat alcohol use disorder (AUD). We recently discovered the first-in-class RXFP3 negative allosteric modulators (NAMs), represented by RLX-33, which significantly reduced alcohol consumption in rats. In this study, we report the design and synthesis of a series of diphenyl-1,2,4-oxadiazole analogues derived from RLX-33. Structure-activity relationship studies of sites A and B of RLX-33 revealed that the aromatic ring at site A is not required for RXFP3 allosteric modulation and the pyrrolidone linker at site B could be replaced with a cyclic or linear alkylamine. Compound (

Indexed as

OxadiazolesPyrrolidinonesReceptors, G-Protein-CoupledRelaxinAllosteric RegulationAnimalsHumansMaleRatsRats, Sprague-DawleyStructure-Activity RelationshipOxadiazolesPyrrolidinonesReceptors, G-Protein-CoupledRelaxinRXFP3 protein, human

Identifiers

PMID40146900
PMCPMC12002401

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Registered trials

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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.