Structural and mechanistic investigation of the acyl-CoA synthetase long-chain family member 4 (ACSL4) inhibition in the context of ferroptosis-related diseases and cancer
(2026)
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- Supervisors
; El Bakali, Jamal- Abstract
- (en) ACSL4 is a key enzyme in lipid metabolism that preferentially activates polyunsaturated fatty acids, contributing to membrane composition and the regulation of metabolic pathways. It is involved in major pathophysiological processes such as ferroptosis and cancer. However, its molecular regulation remains poorly understood due to the lack of selective inhibitors and structural data. This work combined chemical biology, biophysics, and structural biology to develop selective ACSL4 inhibitors and characterize their mechanism of action. An experimental platform enabled the characterization of compounds with improved selectivity and promising cellular effects, as well as the study of their interaction with the enzyme. These compounds serve as pharmacological tools to validate ACSL4 as a therapeutic target. Mechanistic analyses provided insights into their binding mode, enzymatic modulation, and conformational dynamics, paving the way for the rational design of more effective future inhibitors.
- Affiliations
Citations
Mazhari Dorooee, D. (2026). Structural and mechanistic investigation of the acyl-CoA synthetase long-chain family member 4 (ACSL4) inhibition in the context of ferroptosis-related diseases and cancer. https://hdl.handle.net/2078.5/275665