ITRI-126

ITRI-126 is a proteolysis-targeting chimera (PROTAC) designed to degrade the androgen receptor (AR) and its variants, such as AR-V7, for the treatment of castration-resistant prostate cancer (CRPC). Developed by the Industrial Technology Research Institute (ITRI), the molecule is constructed using the core structure of the AR antagonist AZD3514 as the targeting warhead and lenalidomide as the E3 ligase recruiter for cereblon (CRBN), connected via a polyethylene glycol (PEG) linker. ITRI-126 aims to overcome resistance to conventional anti-androgen therapies, like enzalutamide, which often arises from the expression of ligand-binding domain (LBD)-truncated AR variants. Although the compound has demonstrated potent AR degradation in vitro and oral bioavailability, its pharmacokinetic profile has been identified as an area for further optimization.