Unlocking the potential of PROTACs: A comprehensive review of protein degradation strategies in disease therapy

• Published in: Bioorganic chemistry 2023-10, Vol.139, p.106720-106720, Article 106720
• Main Authors: Bhole, Ritesh P., Kute, Payal R., Chikhale, Rupesh V., Bonde, C.G., Pant, Amit, Gurav, Shailendra S.
• Format: Article
• Language: English
• Subjects: Degradation of protein; PROTACs; Ubiquitin proteosome system
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2023.106720

[Display omitted] •PROTACs (PROteolysis TArgeting Chimeras) are a technology used for protein degradation through the use of bifunctional small molecules.•They utilize the ubiquitin–proteasome system (UPS) to induce ubiquitination and subsequent degradation of target proteins.•PROTACs have gained significant attention in the fields of biological studies and therapeutic applications, offering catalytic, reversible, and rapid protein knockdown.•They show promise in treating various disorders, including cancer, immunological disorders, viral diseases, and neurological disorders.•The field of protein degradation has rapidly advanced in recent years, with an increasing number of research articles and clinical-stage small-molecule degraders.•Alongside PROTACs, other degrading technologies such as molecular glue technology are also emerging rapidly.•This review article primarily focuses on different PROTAC molecules designed for specific cellular pathways in various diseases, including cancer, viral diseases, immune disorders, and neurodegenerative diseases.•It discusses new technologies based on PROTACs, such as Antibody PROTAC, Aptamers, Dualtarget, Folatecaged, and TF PROTAC.•The article also provides a list of PROTACs that are currently in clinical trials, highlighting their potential for therapeutic applications. The technology known asPROTACs (PROteolysisTArgeting Chimeras) is a method of protein degradation. Utilising bifunctional small molecules, the ubiquitin-proteosome system (UPS) is used to induce the ubiquitination and degradation of target proteins. In addition to being novel chemical knockdown agents for biological studies that are catalytic, reversible, and rapid, PROTACs used in the treatment for disorders like cancer, immunological disorders, viral diseases, and neurological disorders. The protein degradation field has advanced quickly over the last two years, with a significant rise in research articles on the subject as well as a quick rise in smallmolecule degraders that are currently in or will soon enter the clinical stage. Other new degrading technologies, in addition to PROTAC and molecular glue technology, are also emerging rapidly. In this review article, we mainly focuses on various PROTAC molecules designed with special emphasis on targeted cellular pathways for different diseases i.e., cancer, Viral diseases Immune disorders, Neurodegenerative diseases, etc. We discussed about new technologies based on PROTACs such as Antibody PROTAC