Construction of an IMiD-based azide library as a kit for PROTAC research,Organic & Biomolecular Chemistry

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Construction of an IMiD-based azide library as a kit for PROTAC research
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2020-11-23 , DOI: 10.1039/d0ob02120b
Haixia Liu _{1,

2,

3,

4,

5} , Renhong Sun _{1,

2,

3,

4} , Chaowei Ren _{1,

2,

3,

4,

6} , Xing Qiu _{4,

7,

8,

9,

10} , Xiaobao Yang _{1,

2,

3,

4} , Biao Jiang _{1,

2,

3,

4,

7}

Affiliation

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.

中文翻译：

构建基于IMiD的叠氮化物文库作为PROTAC研究的试剂盒

作为一种有前途的蛋白质降解策略，PROTAC技术正日益成为癌症治疗领域的一颗新星。在这里，我们通过对现有的基于IMiD的胺类库的快速一步转换，报告了基于IMiD的叠氮化物库的有效构建。这个新的叠氮化物文库可以作为试剂盒，通过高效的“点击反应”为PROTAC文库赋予三唑部分用于各种POI，然后帮助快速筛选出对药物开发有价值的铅降解物。已在两种致癌蛋白BCR-ABL和BET上证明了其在快速识别有效降解剂中的作用，该降解剂在降解靶蛋白和有效抑制癌细胞增殖方面显示出与已报道的PROTAC相当或更高的效能。

更新日期：2020-11-23

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