{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hu M"],"funding":["Ningbo Yongjiang Talent Introduction Programme","octoral Program of Entrepreneurship and Innovation in Jiangsu Province","Ningbo Medical Key Discipline","National Natural Science Foundation of China","Zhu Xiu Shan Talent Project of Ningbo No.2 Hospital","Ningbo Natural Science Foundation","Natural Science Foundation of the Jiangsu Higher Education Institutions of China"],"pagination":["406-412"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10945796"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(3)"],"pubmed_abstract":["Ferroptosis is a novel form of oxidative cell death triggered by iron-dependent lipid peroxidation. The induction of ferroptosis presents an attractive therapeutic strategy for human diseases, such as prostate cancer and breast cancer. Herein, we describe our design, synthesis, and biological evaluation of endogenous glutathione peroxidase 4 (GPX4) degraders using the proteolysis targeting chimera (PROTAC) approach with the aim of inducing ferroptosis in cancer cells. Our efforts led to the discovery of compound <b>5i</b> (ZX703), which significantly degraded GPX4 through the ubiquitin-proteasome and the autophagy-lysosome pathways in a dose- and time-dependent manner. Moreover, <b>5i</b> was found to induce the accumulation of lipid reactive oxygen species (ROS) in HT1080 cells, thereby i"],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["ZX703: A Small-Molecule Degrader of GPX4 Inducing Ferroptosis in Human Cancer Cells."],"pmcid":["PMC10945796"],"funding_grant_id":["JSSCBS20210355","2023HMYQ21","2022-F16","21KJB350003","22107051","2022J27"],"pubmed_authors":["Liu H","Li X","Hua H","Xiang Q","Cai T","Zhang Y","Hu M","Sun Y","Zhu D","Wang L"],"additional_accession":[]},"is_claimable":false,"name":"ZX703: A Small-Molecule Degrader of GPX4 Inducing Ferroptosis in Human Cancer Cells.","description":"Ferroptosis is a novel form of oxidative cell death triggered by iron-dependent lipid peroxidation. The induction of ferroptosis presents an attractive therapeutic strategy for human diseases, such as prostate cancer and breast cancer. Herein, we describe our design, synthesis, and biological evaluation of endogenous glutathione peroxidase 4 (GPX4) degraders using the proteolysis targeting chimera (PROTAC) approach with the aim of inducing ferroptosis in cancer cells. Our efforts led to the discovery of compound <b>5i</b> (ZX703), which significantly degraded GPX4 through the ubiquitin-proteasome and the autophagy-lysosome pathways in a dose- and time-dependent manner. Moreover, <b>5i</b> was found to induce the accumulation of lipid reactive oxygen species (ROS) in HT1080 cells, thereby i","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-02T17:25:22.342Z","creation":"2025-04-04T00:28:36.368Z"},"accession":"S-EPMC10945796","cross_references":{"pubmed":["38505849"],"doi":["10.1021/acsmedchemlett.3c00571"]}}