GPX4 catalyzes the reduction of hydrogen peroxide, organic hydroperoxides, and lipid peroxides at the expense of reduced glutathione and functions in the protection of cells against oxidative stress.

In this review, we summarize recent advances in our understanding of the phospholipid repair enzyme GPX4. We examine the molecular mechanisms of GPX4-mediated oxidative regulation, and its potential for therapeutic applications in human diseases.

By detecting the expression change of GPX4 before and after TKI resistance in a variety of LUAD cell lines, we confirmed that the inhibition of GPX4 could overcome epidermal growth factor receptor (EGFR)-TKI resistance by inducing ferroptosis.

The selenoenzyme glutathione peroxidase 4 (GPx4) has been described to control specific cyclooxygenases (COXs) and lipoxygenases (LOXs) that exert substantiated functions in tumor growth and angiogenesis.

Feb 25, 2025 · Glutathione peroxidase 4 (GPX4) is a key metabolic enzyme that reduces lipid peroxide levels, inhibits ferroptosis (a form of programmed cell death characterized by lipid peroxide accumulation), and mitigates inflammation-related lipid signaling [12, 13].

May 1, 2023 · Ubiquitin-proteasome and the CAM are two major systems for GPX4 degradation, altering GPX4 expression. Increased GPX4 inhibits ferroptosis by sensing and reducing lipid peroxidation in the dependent of ALOX15 inhibition, protecting cells from membrane damage and mitochondrial dysfunction.

Jun 11, 2024 · Recent advances in PROTAC technology have resulted in the development of novel PROTAC-based GPX4 degraders aimed at completely inducing GPX4 protein degradation to enhance ferroptosis induction, in contrast to conventional enzyme inhibitors that only inhibit its …

Aug 5, 2024 · Blocking the System X c−_ GSH _ GPX4 pathway to induce ferroptosis in tumor cells is a novel strategy for cancer treatment. GPX4 serves as the core of the System Xc-/GSH/GPX4 pathway and is a predominant target for inducing ferroptosis in tumor cells.

Glutathione Peroxidase 4 (GPX4) is a crucial regulator of ferroptosis that uses glutathione as a cofactor to detoxify cellular lipid peroxidation. Targeting GPX4 in cancer could be a promising strategy to induce ferroptosis and kill drugresistant cancers effectively.

Given GPX4's antitumor effects and the potential of TPD, researchers have explored GPX4-targeting TPDs, which outperform conventional inhibitors in several aspects, such as increased selectivity, strong anti-proliferative effects, overcoming drug …