Targeting GPX4 in ferroptosis and cancer: chemical strategies and challenges

Selenoprotein glutathione peroxidase 4 (GPX4) serves as a crucial suppressor of oxidative stress-induced ferroptosis, making it an attractive target for disease therapy. Here, we discuss recent strategies and challenges associated with targeting GPX4 through covalent inhibitors, proteolysis targetin...

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Published in:Trends in pharmacological sciences (Regular ed.) 2024-08, Vol.45 (8), p.666-670
Main Authors: Liu, Jiao, Tang, Daolin, Kang, Rui
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Enzyme Inhibitors - pharmacology
ferroptosis
Ferroptosis - drug effects
GPX4
Humans
inhibitor
Neoplasms - drug therapy
Neoplasms - metabolism
Neoplasms - pathology
oxidative stress
Oxidative Stress - drug effects
Phospholipid Hydroperoxide Glutathione Peroxidase - antagonists & inhibitors
Phospholipid Hydroperoxide Glutathione Peroxidase - metabolism
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creator Liu, Jiao
Tang, Daolin
Kang, Rui
description Selenoprotein glutathione peroxidase 4 (GPX4) serves as a crucial suppressor of oxidative stress-induced ferroptosis, making it an attractive target for disease therapy. Here, we discuss recent strategies and challenges associated with targeting GPX4 through covalent inhibitors, proteolysis targeting chimera (PROTAC) degraders, and cell-type-specific degraders in the context of cancer. Selenoprotein glutathione peroxidase 4 (GPX4) serves as a crucial suppressor of oxidative stress-induced ferroptosis, making it an attractive target for disease therapy. Here, we discuss recent strategies and challenges associated with targeting GPX4 through covalent inhibitors, proteolysis targeting chimera (PROTAC) degraders, and cell-type-specific degraders in the context of cancer.
doi_str_mv 10.1016/j.tips.2024.05.006
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subjects Animals
Antineoplastic Agents - pharmacology
Enzyme Inhibitors - pharmacology
ferroptosis
Ferroptosis - drug effects
GPX4
Humans
inhibitor
Neoplasms - drug therapy
Neoplasms - metabolism
Neoplasms - pathology
oxidative stress
Oxidative Stress - drug effects
Phospholipid Hydroperoxide Glutathione Peroxidase - antagonists & inhibitors
Phospholipid Hydroperoxide Glutathione Peroxidase - metabolism
title Targeting GPX4 in ferroptosis and cancer: chemical strategies and challenges
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