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.
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http://dx.doi.org/10.1016/j.bioorg.2023.106720 | DOI Listing |
Front Biosci (Elite Ed)
October 2024
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, 1983969411 Tehran, Iran.
Background: Regenerative endodontics requires an innovative delivery system to release antibiotics/growth factors in a sequential trend. This study focuses on developing/characterizing a thermoresponsive core-shell hydrogel designed for targeted drug delivery in endodontics.
Methods: The core-shell chitosan-alginate microparticles were prepared by electrospraying to deliver bone morphogenic protein-2 for 14 days and transforming growth factor-beta 1 (TGF-β1) for 7-14 days.
Front Biosci (Landmark Ed)
December 2024
Department of Cardiovascular Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, 410008 Changsha, Hunan, China.
Background: Chronic heart failure (CHF) is a serious cardiovascular condition. Vascular peroxidase 1 (VPO1) is associated with various cardiovascular diseases, yet its role in CHF remains unclear. This research aims to explore the involvement of VPO1 in CHF.
View Article and Find Full Text PDFJ Integr Neurosci
December 2024
Department of Human Anatomy, School of Basic Medical Sciences, Wannan Medical College, 241002 Wuhu, Anhui, China.
Background: K48-linked ubiquitin chain (Ub-K48) is a crucial ubiquitin chain implicated in protein degradation within the ubiquitin-proteasome system. However, the precise function and molecular mechanism underlying the role of Ub-K48 in the pathogenesis of Alzheimer's disease (AD) and neuronal cell abnormalities remain unclear. The objective of this study was to examine the function of K48 ubiquitination in the etiology of AD, and its associated mechanism of neuronal apoptosis.
View Article and Find Full Text PDFJACS Au
December 2024
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, No. 345 Lingling Road, Shanghai 200032, China.
Macrocyclization is a compelling strategy for conventional drug design for improving biological activity, target specificity, and metabolic stability, but it was rarely applied to the design of PROTACs possibly due to the mechanism and structural complexity. Herein, we report the rational design of the first series of "Head-to-Tail" macrocyclic PROTACs. The resulting molecule exhibited pronounced Brd4 protein degradation with low nM DC values while almost totally dismissing the "hook effect", which is a general character and common concern of a PROTAC, in multiple cancer cell lines.
View Article and Find Full Text PDFOncol Res
December 2024
Department of Biology, College of Science, Sultan Qaboos University, Muscat, 123, Oman.
Nanotechnology in cancer therapy has significantly advanced treatment precision, effectiveness, and safety, improving patient outcomes and personalized care. Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells, precisely sensing the tumor microenvironment (TME) and sparing normal cells. These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation, and they can also overcome therapy resistance and deliver multiple drugs simultaneously.
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