TG-TW-0288

TG-TW-0288 is a peptide-based proteolysis-targeting chimera (PROTAC) designed to selectively degrade glutathione peroxidase 4 (GPX4) to induce ferroptosis in prostate cancer cells [1]. It consists of a GPX4-targeting peptide conjugated to a Siah E3 ubiquitin protein ligase 1 (SIAH1)-binding motif via a GGSGG linker [1]. By leveraging SIAH1, an E3 ligase overexpressed in prostate cancer, TG-TW-0288 achieves tumor-selective protein degradation [1]. To enhance cellular uptake and efficacy, it can be loaded onto gold nanoparticles (Au NPs) to form TG-TW-0288@Au [1]. Preclinical studies demonstrate that TG-TW-0288@Au effectively degrades GPX4, activates ferroptosis, reduces cell viability, and suppresses tumor growth in prostate cancer xenograft models [1].