ATB-238

ATB-238 is a second-generation Androgen Receptor (AR) targeting AUTOTAC (Autophagy-Targeting Chimera) designed for the treatment of castrate-resistant prostate cancer (CRPC). It functions as a targeted protein degrader that recruits the autophagy-lysosomal pathway to eliminate the androgen receptor and its splice variants, such as AR-v7, which are often responsible for therapeutic resistance to conventional AR-targeting therapies. ATB-238 consists of a target-binding ligand and an autophagy-targeting ligand that induces the formation of an AR:p62 complex by binding to the ZZ domain of the p62 protein. This leads to the degradation of AR isoforms and the reduction of AR transcriptional activity. Developed as an advancement over first-generation AUTOTACs, ATB-238 has demonstrated potent cytotoxicity in AR-positive prostate cancer models and shows synergistic effects when combined with docetaxel.