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

Ritesh P Bhole, Payal R Kute, Rupesh V Chikhale, C G Bonde, Amit Pant, Shailendra S Gurav

Journal: Bioorganic chemistry 2023;139():106720

PMID: 37480814

Full Text on Elsevier Science View on PubMed

Abstract

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, Aptamers, Dual target, Folate caged, TF PROTAC, etc. Also, we listed out the PROTACs which are in clinical trials.

Address: Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra 411018, India. Electronic address: [email protected].; Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra 411018, India.; UCL School of Pharmacy, London, United Kingdom. Electronic address: [email protected].; Department of Pharmaceutical Chemistry, School of Pharmacy & Technology Management, SVKM's NMIMS, Shirpur Campus 425 405, India. Electronic address: [email protected].; School of Medicine Creighton University, Omaha, Neraska, USA. Electronic address: [email protected].; Department of Pharmacognosy, Goa College of Pharmacy, Panaji, Goa University, Goa 403001, India. Electronic address: [email protected].

DOI: 10.1016/j.bioorg.2023.106720

Link outs

Free resources

Miscellaneous:

https://assays.cancer.gov/non-CPTAC-1157

Subscription / membership required

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S0045...

MeSH Terms: Proteolysis, Proteolysis Targeting Chimera, Proteasome Endopeptidase Complex, Antibodies, Catalysis