Construction of an IMiD-based azide library as a kit for PROTAC research

Haixia Liu; Renhong Sun; Chaowei Ren; Xing Qiu; Xiaobao Yang; Biao Jiang

doi:10.1039/D0OB02120B

Construction of an IMiD-based azide library as a kit for PROTAC research†

Haixia Liu,‡^abc Renhong Sun,‡^a Chaowei Ren,^acd Xing Qiu,^e Xiaobao Yang

*^a and Biao Jiang*^ae

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* Corresponding authors

^a Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, China
E-mail: jiangbiao@shanghaitech.edu.cn, yangxb@shanghaitech.edu.cn

^b School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, China

^c University of Chinese Academy of Sciences, Beijing 100049, China

^d School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, China

^e CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China

Abstract

As a promising protein degradation strategy, PROTAC technology is increasingly becoming a new star in cancer treatment. Here we report the efficient construction of an IMiD-based azide library via a quick one-step conversion of the existing IMiD-based amine library. This new azide library can act as a kit to endow PROTAC libraries with triazole moieties for various POIs through a highly effective ‘click reaction’ and then help to rapidly screen out lead degraders that are valuable for drug development. Its power in fleetly identifying potent degraders has been verified on two oncogenic proteins, BCR-ABL and BET, the degraders of which showed comparable potency to or even higher potency than the reported PROTACs in degrading target proteins and effectively inhibiting cancer cell proliferation.

This article is part of the themed collections: Bioorthogonal and click chemistry: Celebrating the 2022 Nobel Prize in Chemistry and Chemical Biology in OBC

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DOI: https://doi.org/10.1039/D0OB02120B
Article type: Communication
Submitted: 20 Oct 2020
Accepted: 16 Nov 2020
First published: 23 Nov 2020

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Org. Biomol. Chem., 2021,19, 166-170

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Construction of an IMiD-based azide library as a kit for PROTAC research

H. Liu, R. Sun, C. Ren, X. Qiu, X. Yang and B. Jiang, Org. Biomol. Chem., 2021, 19, 166 DOI: 10.1039/D0OB02120B

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Organic & Biomolecular Chemistry

Construction of an IMiD-based azide library as a kit for PROTAC research†

Abstract

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Construction of an IMiD-based azide library as a kit for PROTAC research

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