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

Proteolysis-Targeting Chimeras (PROTACs) represent a significant advancement in drug discovery by enabling the targeted degradation of disease-driving proteins, including those previously considered "undruggable." Since the first PROTAC entered trials in 2019, the technology has shown promise in oncology, neurodegenerative diseases, metabolic disorders, and inflammatory conditions. PROTACs offer a unique pharmacological advantage by leveraging the ubiquitin-proteasome system for protein degradation, distinguishing them from traditional therapies. Despite challenges such as oral bioavailability and resistance mechanisms, innovative delivery strategies and expanding E3 ligase repertoires are being developed to overcome these hurdles. With over 50 candidates in clinical trials and some reaching Phase III, PROTACs are poised to become central to future therapeutic strategies, offering safer and more effective treatments for various diseases. Notably, trials like GT20029 for androgenetic alopecia have shown good safety and efficacy, highlighting the potential of PROTACs in diverse medical fields.