Proteolysis-Targeting Chimera (PROTAC): Current Applications And Future Directions

Proteolysis-targeting chimeras (PROTACs) represent a significant advancement in targeted protein degradation, offering new therapeutic possibilities for previously "undruggable" targets. This review highlights the development of PROTACs across various therapeutic areas, focusing on key targets like kinases and hormone receptors. Notable candidates include ARV-110 for prostate cancer and ARV-471 for breast cancer, with clinical trials progressing to Phase III by 2024. Challenges such as the "hook effect" and oral bioavailability are discussed, alongside future directions like innovative delivery strategies and expanding E3 ligase repertoires. The review underscores the potential of PROTACs to transform treatments for complex diseases resistant to traditional therapies.