GPX4-AUTAC

Description

GPX4-AUTAC is a GPX4-targeting autophagy-mediated degrader AUTAC . GPX4-AUTAC consists of an inhibitor ML162-yne HY-153748 , a degradation tag FBnG HY-W073762 and a glycol linker HY-W021401 . GPX4-AUTAC promotes the ubiquitination of GPX4 by E3 ligase TRAF6, and enhances the binding with GPX4 and p62, leading to the selective autophagy-dependent degradation of GPX4. GPX4-AUTAC significantly induces ferroptosis and shows a potent anti-cancer activity in breast cancer cells, breast cancer-derived organoids PDOs and MDA-MB-231 tumor xenograft mice model, with potent synergistic effects when combined with Sulfasalazine SAS HY-14655 or chemotherapy drugs Paclitaxel HY-B0015 or Cisplatin HY-17394 .