Construction of PROTAC Library via Liquid-Phase Synthesis Enabled by a Hydrophobic Tag

Organic Letters 2026

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Authors: Yifeng Zhou, Wei He, Zehui Zhou, Min Huan Wu, Qianping Wu, Zhaofan Tao, Mingyue Zheng, Sulin Zhang, Tianfeng Xu
DOI: 10.1021/acs.orglett.6c00263
Cited by: 0
References: 28

Abstract

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 25 emerged as the most potent one, exhibiting a subnanomolar DC 50 value, high D max, and strong antiproliferative activity.

Fields of Study & Subjects

Protein Degradation and Inhibitors Chemical Synthesis and Analysis Prostate Cancer Treatment and Research

Publication details

Journal / source
Organic Letters
Volume
28
Issue
8
Pages
2747–2752
Publication date
12 February 2026
Language
EN