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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Hydrophobic Tag Tethering Degradation, The Emerging Targeted Protein Degradation Strategy

Author(s): Jieke Gao, Jiantao Zhang, Xiaoli Han and Jinming Zhou*

Volume 30, Issue 27, 2023

Published on: 14 November, 2022

Page: [3137 - 3155] Pages: 19

DOI: 10.2174/0929867329666220930120328

Price: $65


Targeted protein degradation (TPD) strategies have become a new trend in drug discovery due to the capability of triggering the degradation of protein of interest (POI) selectively and effectively in recent decades. Particularly, the hydrophobic tag tethering degrader (HyTTD) has drawn a lot of attention and may offer a promising strategy for new drug research and development in the future. Herein, we will give an overview of the development of HyTTD, the structure-activity relationship (SAR) between HyTTD and linkers, HyTs, and ligand motifs, as well as the various HyTTDs targeting different targets, thus offering a rational strategy for the design of HyTTDs in further TPD drug discovery.

Keywords: Targeted protein degradation, hydrophobic tag tethering degrader, hydrophobic tag, drug discovery, structure-activity relationship, HyTTDs.

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