Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 64, Issue 9, Pages 5252-5275Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.0c01914
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Funding
- Novo Nordisk Foundation [NNF19OC0055818, NNF17OC0028366, NNF19OC0058183]
- Carlsberg Foundation [CF19-0072, CF19-0295]
- DTU
- Independent Research Fund Denmark [904100241B, 9041-00248B]
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Reactive oxygen species (ROS) play vital roles in physiological cellular processes, and maintaining appropriate levels of cellular ROS is important for redox homeostasis. Directly targeting the sources of ROS production has become a key focus in research due to the potential link between high ROS concentrations and severe diseases.
Reactive oxygen species (ROS) are involved in physiological cellular processes including differentiation, proliferation, and apoptosis by acting as signaling molecules or regulators of transcription factors. The maintenance of appropriate cellular ROS levels is termed redox homeostasis, a balance between their production and neutralization. High concentrations of ROS may contribute to severe pathological events including cancer, neuro-degenerative, and cardiovascular diseases. In recent years, approaches to target the sources of ROS production directly in order to develop tool compounds or potential therapeutics have been explored. Herein, we briefly outline the major sources of cellular ROS production and comprehensively review the targeting of these by small-molecule inhibitors. We critically assess the value of ROS inhibitors with different mechanisms-of-action, including their potency, mode-of-action, known off-target effects, and clinical or preclinical status, while suggesting future avenues of research in the field.
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