Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, P.R. China.
Drug Development and Innovation Center, College of Chemistry and Life Sciences, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, P.R. China.
Curr Med Chem. 2023;30(27):3137-3155. doi: 10.2174/0929867329666220930120328.
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.
靶向蛋白降解（TPD）策略在近几十年来因其能够选择性和有效地引发靶蛋白（POI）降解而成为药物发现的新趋势。特别是疏水标签连接降解剂（HyTTD）引起了广泛关注，可能为未来新药研究和开发提供有前景的策略。在此，我们将概述 HyTTD 的发展、HyTTD 与连接子、HyTs 和配体基序之间的结构-活性关系（SAR），以及针对不同靶标的各种 HyTTD，从而为进一步的 TPD 药物发现中 HyTTD 的设计提供合理策略。
