GDCNF-11

GDCNF-11 (0.03-3 μM; 2-24 h, 24 h treatment followed by 0-24 h washout) potently degrades GPX4 in HT-1080 cells with a DC₅₀ of 0.08 μM, following a time-dependent pattern with transient early upregulation and sustained post-washout activity for 12 h^[1].
GDCNF-11 (0.1-1 μM; 24 h) does not alter GPX4 mRNA expression in HT-1080 cells, indicating it acts by degrading GPX4 protein rather than modulating transcription^[1].
GDCNF-11 binds to recombinant human HSP90α with high affinity, with a Kd value of 0.19 μM; it inhibits the growth of HT-1080 cells, with an IC₅₀ of 0.74 μM; and its cytotoxicity is mainly mediated by ferroptosis^[1].
GDCNF-11 (0.3-1 μM; 24 h, 2 h pretreatment) induces proteasome-dependent GPX4 degradation in HT-1080 cells via HSP90 (both α and β isoforms) recruitment, ternary complex formation, and ubiquitination mediated by cullin E3 ligases including CUL5 and CHIP^[1].
GDCNF-11 forms a stable ternary complex with HSP90 and GPX4 via conserved ligand-protein interactions and additional inter-protein contacts, supporting its mechanism of action as an HIM-PROTAC^[1].
GDCNF-11 (1 μM; 24 h) exhibits high selectivity for GPX4 degradation in HT-1080 cells, with only a small number of additional proteins significantly altered, including upregulated HMOX1^[1].
GDCNF-11 (varied; 12 h) dose-dependently increases intracellular lipid peroxidation in HT-1080 cells, an effect that is abrogated by ferroptosis inhibitor Fer-1, consistent with ferroptosis induction^[1].
GDCNF-11 (1 μM; 24 h) induces a significant increase in intracellular ROS and Fe²⁺ levels in HT-1080 cells, consistent with ferroptosis activation^[1].
GDCNF-11 (1 μM; 24 h) induces ferroptosis-specific mitochondrial morphological changes and autophagosome-like structures in HT-1080 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.