Synthesis and biological evaluation of thiazole derivatives as novel USP7 inhibitors
Synthesis and biological evaluation of thiazole derivatives as novel USP7 inhibitors
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新型USP7抑制剂噻唑衍生物的合成及生物学评价
DOI：
10.1016/j.bmcl.2017.01.018
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发表时间：
2017-02-15
影响因子：
2.7
通讯作者：
Wen, Xiaoan
中科院分区：
文献类型：
--
作者：
Chen, Chao;Song, Jiemei;Wen, Xiaoan
疱疹病毒相关泛素特异性蛋白酶（HAUSP，也称为USP7）与Mdm2相互作用并稳定Mdm2，代表了去泛素酶致癌蛋白的第一个例子之一。USP7被认为是癌症治疗的潜在药物靶点。USP7的抑制剂最近在体外和体内被证明可以抑制肿瘤细胞的生长。以USP7抑制剂P5091和P22077为基础，设计并合成了一系列噻唑衍生物。体外实验结果表明，噻唑类化合物对USP7酶和癌细胞均表现出较低的微摩尔抑制活性。这些化合物以p53依赖和p53不依赖的方式诱导细胞死亡。综上所述，本研究可能为一类新的USP7抑制剂提供噻唑类化合物。(C) 2017 Elsevier Ltd.版权所有。
Herpesvirus-associated Ubiquitin-Specific Protease (HAUSP, also called USP7) interacts with and stabilizes Mdm2, and represents one of the first examples that deubiquitinases oncogenic proteins. USP7 has been regarded as a potential drug target for cancer therapy. Inhibitors of USP7 have been recently shown to suppress tumor cell growth in vitro and in vivo. Based on leading USP7 inhibitors P5091 and P22077, we designed and synthesized a series of thiazole derivatives. The results of in vitro assays showed that the thiazole compounds exhibited low micromolar inhibition activity against both USP7 enzyme and cancer cell lines. The compounds induced cell death in a p53-dependent and p53-independent manner. Taken together, this study may provide thiazole compounds as a new class of USP7 inhibitors. (C) 2017 Elsevier Ltd. All rights reserved.