GPX4-AUTAC

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) ) [1].

Product Specifications

CAS Number

[3060458-90-1]

UNSPSC

12352005

Target

AUTACs; Autophagy; Ferroptosis; Glutathione Peroxidase

Related Pathways

Apoptosis; Autophagy; Metabolic Enzyme/Protease; PROTAC

Applications

Metabolism-sugar/lipid metabolism

Field of Research

Cancer

Smiles

O=C(C(N(C1=CC(Cl)=C(OCC(N=N2)=CN2CCOCCOCCOCCNC([C@H](CSC3=NC4=C(N3CC5=CC=C(C=C5)F)N=C(NC4=O)N)NC(C)=O)=O)C=C1)C(CCl)=O)C6=CC=CS6)NCCC7=CC=CC=C7

Molecular Formula

C50H55Cl2FN12O9S2

Molecular Weight

1122.08

References & Citations

[1]Gong R, et al. GPX4-AUTAC induces ferroptosis in breast cancer by promoting the selective autophagic degradation of GPX4 mediated by TRAF6-p62. Cell Death Differ. 2025 May 20.