Investigating the acyl-CoA synthetase long-chain family member 4 (ACSL4) inhibition and substrate specificity : a pathway to targeting ferroptosis-related diseases and cancer
(2025)
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- Abstract
- ACSL4 is a key enzyme in lipid metabolism that preferentially activates polyunsaturated fatty acids (PUFAs), channeling them into various metabolic pathways. Through this specificity, it regulates the synthesis of lipid mediators such as eicosanoids and influences the properties of cellular membranes. These functions place it at the center of major physiopathological processes, including inflammation, ferroptosis, and cancer. The first part of this work focused on developing new small-molecule ACSL4 inhibitors, more potent and selective than reference compounds, which will serve as tools to validate ACSL4 as a therapeutic target and potentially inspire future drugs. In the second part, we explored the biochemical and biophysical parameters determining ACSL4 specificity for PUFAs and identified an original mechanism of product inhibition regulating substrate selection by the enzyme
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Marteau, R. (2025). Investigating the acyl-CoA synthetase long-chain family member 4 (ACSL4) inhibition and substrate specificity : a pathway to targeting ferroptosis-related diseases and cancer. https://hdl.handle.net/2078.5/248999