PROTACs: Promising approach for anticancer therapy. (1st March 2023)

• Record Type: Journal Article
• Authors: Kaur, Simran Deep; Bedi, Neena; Kumar, Deepak; Kapoor, Deepak N.
• Is Part Of: Cancer letters. Volume 556(2023)
• Publication Date: 2023-03-01
• Subjects: Proteolysis targeting chimeras (PROTACs) -- Protein of interest (POI) -- Bromodomain-containing protein 4 (BRD4) -- Galactose-decorated liver tumor-specific nanoliposomes (GALARV); Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2023.216065
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Proteolysis-targeting chimeras (PROTACs) are being developed as an effective method for degrading cancer-related proteins by modifying the endogenous ubiquitin-proteasome system. To investigate the dynamics between an E3 ligase and target protein, researchers have developed a wide variety of bifunctional PROTACs by combining small molecule ligands. These PROTACs employ numerous ligands, some of which are reversible, some of which are irreversible, some attach to orthosteric sites, while others bind to allosteric sites. Some are agonists, while others are antagonists, and the target protein may be activated in either a positive or negative manner. A variety of targeted ligand approaches can be used to enhance PROTAC properties, including tumor selectivity and drug delivery, and to overcome drug resistance. The processes and behaviors of small molecule-based PROTACs and targeted proteolysis approaches as anticancer therapeutic molecules have been introduced in this mini-review. Graphical abstract: PROTACs approach for anticancer therapy Image 1 Highlights: Proteolysis Targeting Chimeras (PROTACs) are relatively new and potentially useful therapeutic approaches. PROTACs have two active sites that coordinate to initiate proteolysis of a target protein through ubiquitin E3 ligase pathway. The ubiquitin E3 ligase is connected to the protein-of-interest through an appropriate linker to form a PROTAC molecule. Targeting and stimulus-responsive PROTACs are developed by various design strategies including prodrugs and nanoparticles.