Synthesis and Biological Evaluation of 9-Oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile Analogues as Potential Inhibitors of Deubiquitinating Enzymes
Synthesis and Biological Evaluation of 9-Oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile Analogues as Potential Inhibitors of Deubiquitinating Enzymes
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DOI：
10.1002/cmdc.200900409
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发表时间：
2010-04-01
期刊：
影响因子：
3.4
通讯作者：
Guedat, Philippe
中科院分区：
文献类型：
--
作者：
Colombo, Matteo;Vallese, Stefania;Guedat, Philippe
高通量筛选强调了9-氧代-9H-茚并[1，2-B]吡嗪-2，3-二甲腈（1）作为泛素特异性蛋白酶（USP）的活性抑制剂，USP是一种参与从蛋白质底物中去除泛素的水解酶家族。研究了化合物1的化学行为。此外，新化合物的合成和体外评价，1的类似物，导致去泛素化酶USP 8的有效和选择性抑制剂的鉴定。
High-throughput screening highlighted 9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile (1) as an active inhibitor of ubiquitin-specific proteases (USPs), a family of hydrolytic enzymes involved in the removal of ubiquitin from protein substrates. The chemical behavior of compound 1 was examined. Moreover, the synthesis and in vitro evaluation of new compounds, analogues of 1, led to the identification of potent and selective inhibitors of the deubiquitinating enzyme USP8.