Construction of PROTAC Library via Liquid-Phase Synthesis Enabled by a Hydrophobic Tag
Herein, we present a new synthetic strategy for PROTAC development by using hydrophobic tag-assisted liquid-phase synthesis (LPS). The hydrophobic tag enables intermediates to be purified by precipitation, thus sparing the effort of column purification. Adopting this strategy, we efficiently constructed highly diverse linker and androgen receptor (AR)-targeting PROTAC libraries. Among the 26 synthesized PROTACs, compound <b>25</b> emerged as the most potent one, exhibiting a subnanomolar DC<sub>50</sub> value, high <i>D</i><sub>max</sub>, and strong antiproliferative activity.
Authors
- Zehui Zhou (ORCID: https://orcid.org/0000-0001-6093-6255)
- Min Wu (ORCID: https://orcid.org/0000-0001-5462-6920)
- Shufen Zhang (ORCID: https://orcid.org/0000-0003-3390-4199)
- Qianping Wu
- Zhaofan Tao
- Mingyue Zheng
- Tianfeng Xu
- Yifeng Zhou
- Wei He
Institutions
- Chinese Academy of Sciences (CN)
- Shanghai Institute of Materia Medica (CN)
- Drug Discovery Laboratory (Norway) (NO)
- Institute for Advanced Study (DE)
- University of Chinese Academy of Sciences (CN)
- State Key Laboratory of Drug Research
Publication Details
- Journal
- Organic Letters
- Published
- 2026-02-12
- DOI
- https://doi.org/10.1021/acs.orglett.6c00263
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.00