Evidence map›Paper›PMID 42446538›Full record

ArticleMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents2026

Novel P2X4 Receptor Antagonist MRS4719 Improves Ischemia/reperfusion Injury in Mice.

Rajkumar Verma, Jinting Zhang, Sanjeev Kumar Yadav, Jianlin Feng, Chunxia C Cronin, Daylin Gamiotea-Turro, Kiran S Toti, Zhiwei Wen, Kenneth A Jacobson, Bruce T Liang

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Article in Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents, 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
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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

10 authors.

Rajkumar VermaDepartment of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, 06030, USA. raverma@uchc.edu.ORCID http://orcid.org/0000-0002-1123-6508
Jinting ZhangPat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Sanjeev Kumar YadavDepartment of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Jianlin FengPat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Chunxia C CroninPat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Daylin Gamiotea-TurroDepartment of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Kiran S TotiNIDDK, National Institutes of Health, Bethesda, MD, 20892, USA.
Zhiwei WenNIDDK, National Institutes of Health, Bethesda, MD, 20892, USA.
Kenneth A JacobsonNIDDK, National Institutes of Health, Bethesda, MD, 20892, USA.
Bruce T LiangPat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, 06030, USA. Bliang@uchc.edu.

Funding

Development of Drugs Acting at Ion ChannelsZIADK031127 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI JACOBSON, KENNETH ALAN · 2009 to 2025
$3.9M
Therapeutic implications of purinergic receptor P2X4 in ischemic strokeR01NS125405 · NINDS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI Rajkumar Verma · 2022 to 2026
$2.5M
A New Drug Therapy for Advanced Heart FailureR44HL152710 · NHLBI · CORNOVUS PHARMACEUTICALS, INC. · PI VAN ALLEN, R MARK · 2020 to 2021
$2.0M
PURINERGIC SIGNALING IN CULTURED HEART CELLSR01HL048225 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LIANG, BRUCE T · 1993 to 2005
$1.9M
American Heart Association-American Stroke Association 18CDA34110011Intramural NIH HHS ZIA DK031127NHLBI NIH HHS HL48225 and HL152710NHLBI NIH HHS R01 HL048225NHLBI NIH HHS R44 HL152710NIDDK Intramural Research Program ZIADK31127NINDS NIH HHS 1R01NS125405NINDS NIH HHS R01 NS125405
6 · The paper itself

Abstract

Ischemic injury triggers extracellular ATP release, activating P2X4 receptors (P2 × 4R) on immune and cardiac cells, which exacerbates inflammation and tissue damage. We evaluated MRS4719, a selective P2 × 4R antagonist, in aged mice subjected to transient middle cerebral artery occlusion (tMCAo) and cardiac ischemia/reperfusion (CI/R) injury. MRS4719 exhibited a nonlinear dose response, with an intermediate dose (2.25 mg/kg/day) and short-term treatment (2 days) optimally improving sensorimotor and cognitive recovery while reducing brain tissue atrophy. Treatment initiated up to 12 h post-stroke significantly decreased infarct volume. Additionally, MRS4719 preserved cardiac contractile function following ischemia/reperfusion injury. These findings suggest that targeted P2X4R inhibition mitigates inflammatory injury across multiple organs and supports functional recovery, highlighting MRS4719's therapeutic potential for cerebral and cardiac ischemic disorders.

Identifiers

PMID42446538
PMCPMC13445571

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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.