Research advances in small-molecule hydrophobic tagging protein degraders
10.11665/j.issn.1000-5048.2024031301
- VernacularTitle:小分子疏水标签蛋白降解剂的研究进展
- Author:
Zirui HUO
1
;
Jieyu PEI
;
Fangyi ZHAN
;
Shaowen XIE
;
Jinyi XU
;
Shengtao XU
Author Information
1. 中国药科大学药物化学系, 南京 211198
- Publication Type:Journal Article
- Keywords:
hydrophobic tag;
targeted protein degradation;
adamantane;
cancer
- From:
Journal of China Pharmaceutical University
2025;56(2):252-263
- CountryChina
- Language:Chinese
-
Abstract:
In In recent years, small-molecule targeted protein degraders inducing protein degradation have been developing rapidly. These molecules are attracting substantial interest from researchers since they can overcome such limitations of traditional small-molecule inhibitors as their inapplicability to ‘undruggable’ targets and tendency to induce drug resistance. Compared with other targeted protein degraders, small-molecule hydrophobic tags (HyTs) may have a smaller number of hydrogen bond donors/acceptors, smaller molecular weights, and better pharmacokinetic profiles, thus attracting extensive attention from researchers. This review focuses on the possible mechanisms and popular types of HyTs, with special attention to the potential application value of adamantane, a typical hydrophobic tag, in the fields of cancer and neurodegeneration. In general, there are still some problems like fewer types of hydrophobic tags and insufficient research on degradation mechanisms, which still need to be further explored. This review is expected to provide researchers working in the fields of small-molecule targeted protein degraders with some valuable reference.
