Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
Novel P2X4 Receptor Antagonist MRS4719 Improves Ischemia/reperfusion Injury in Mice.
СтатьяНазвание и аннотация: Перевод в очереди
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Verma Rajkumar, Zhang Jinting, Yadav Sanjeev Kumar, Feng Jianlin, Cronin Chunxia C, Gamiotea-Turro Daylin, Toti Kiran S, Wen Zhiwei, Jacobson Kenneth A, Liang Bruce T
Аннотация
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.