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Review
. 2025 Sep 13;14(18):6465.
doi: 10.3390/jcm14186465.

Targeting Mitochondrial Reactive Oxygen Species: JP4-039's Potential as a Cardiovascular Therapeutic

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Free article
Review

Targeting Mitochondrial Reactive Oxygen Species: JP4-039's Potential as a Cardiovascular Therapeutic

Keertana Yalamanchili et al. J Clin Med. .
Free article

Abstract

JP4-039, a mitochondrial-targeted nitroxide, has emerged as a promising candidate in addressing the intricate interplay of reactive oxygen species (ROS) in cardiovascular disease (CVD). Given the substantial mortality and economic burden associated with CVD globally, novel therapeutic strategies targeting oxidative stress hold significant promise. The pathophysiology of CVD encompasses multifaceted mechanisms, including endothelial dysfunction, inflammation, and oxidative stress, where dysregulated ROS levels play a pivotal role. JP4-039, by selectively targeting mitochondrial ROS, offers a targeted approach to mitigate oxidative stress-induced damage in cardiovascular tissue. Current research elucidates the molecular mechanisms underlying JP4-039's antioxidant properties, including its ability to scavenge superoxide radical anions and mitigate oxidative chain reactions within mitochondria. Moreover, preclinical studies highlight JP4-039's efficacy in ameliorating CVD-related pathologies, including atherosclerosis and cardiac hypertrophy, through its antioxidative and anti-inflammatory effects. Future milestones in JP4-039 research involve optimizing its pharmacokinetic (PK) properties and exploring potential synergistic effects with existing cardiovascular therapies, followed by advancing into clinical trials.

Keywords: JP4-039; cardiovascular disease; mitochondrial antioxidants; reactive oxygen species.

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