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Current Drug Targets

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ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

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Review Article

N-Heterocycle based Degraders (PROTACs) Manifesting Anticancer Efficacy: Recent Advances

Author(s): Suddhasatwa Banerjee, Sachin Sharma, Amandeep Thakur, Ritika Sachdeva, Ram Sharma, Kunal Nepali* and Jing Ping Liou*

Volume 24, Issue 15, 2023

Published on: 08 November, 2023

Page: [1184 - 1208] Pages: 25

DOI: 10.2174/0113894501273969231102095615

Price: $65

Abstract

Proteolysis Targeting Chimeras (PROTACs) technology has emerged as a promising strategy for the treatment of undruggable therapeutic targets. Researchers have invested a great effort in developing druggable PROTACs; however, the problems associated with PROTACs, including poor solubility, metabolic stability, cell permeability, and pharmacokinetic profile, restrict their clinical utility. Thus, there is a pressing need to expand the size of the armory of PROTACs which will escalate the chances of pinpointing new PROTACs with optimum pharmacokinetic and pharmacodynamics properties. N- heterocycle is a class of organic frameworks that have been widely explored to construct new and novel PROTACs. This review provides an overview of recent efforts of medicinal chemists to develop N-heterocycle-based PROTACs as effective cancer therapeutics. Specifically, the recent endeavors centred on the discovery of PROTACs have been delved into various classes based on the E3 ligase they target (MDM2, IAP, CRBN, and other E3 ligases). Mechanistic insights revealed during the biological assessment of recently furnished Nheterocyclic- based PROTACs constructed via the utilization of ligands for various E3 ligases have been discussed.

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