Inhibition of androgen receptor (AR) has been extensively investigated to treat prostate cancer. Resistance mechanisms such as increased levels of androgen production, increased AR gene, enhancer expression and AR point mutations always reduce the clinical efficacy. Design and discovery of small-molecule PROTAC AR degraders have been pursued as a new therapeutic strategy to overcome common resistance mechanisms developed during prostate cancer treatment. In the last two decades, potent and eļ¬cacious PROTAC AR degraders have been gotten rapid development and several such compounds have been advanced into preclinical phase and phase I/II trials for the treatment of human prostate cancers. Especially, the first PROTAC to enter the clinic, ARV-110, has shown good clinical effects in patients with mCRPC. This fully demonstrates the high clinical value of PROTAC strategy in treatment of human diseases. Here, we summarized the recent advances in the development of these potential clinical-stage PROTAC AR degraders.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022 Dec 09 [Epub]
Xiaojuan Jia, Xin Han
The 2nd Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China., The 2nd Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310029, China.. Electronic address: .