Discovery of indirubin derivatives as new class of DRAK2 inhibitors from high throughput screening
Discovery of indirubin derivatives as new class of DRAK2 inhibitors from high throughput screening
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DOI：
10.1016/j.bmcl.2016.03.111
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发表时间：
2016-06-01
影响因子：
2.7
通讯作者：
Choi, Gildon
中科院分区：
文献类型：
--
作者：
Jung, Myoung Eun;Byun, Byung Jin;Choi, Gildon
DRAK 2是属于死亡相关蛋白激酶（DAPK）家族的丝氨酸/苏氨酸激酶，并且已经成为用于治疗自身免疫性疾病和癌症的有前景的药物靶标。为了鉴定DRAK 2的小分子抑制剂，我们使用内部化学文库进行了高通量筛选活动，并将靛玉红-3 '-单肟鉴定为新型DRAK 2抑制剂。在测试的化合物中，化合物16显示出对DRAK 2最有效的抑制活性（IC 50 = 0.003 μ M）。基于酶动力学和分子对接研究，我们还提出化合物16可能与酶的ATP结合位点结合。(C)2016爱思唯尔有限公司版权所有。
DRAK2 is a serine/threonine kinase belonging to the death- associated protein kinase (DAPK) family and has emerged as a promising drug target for the treatment of autoimmune diseases and cancers. To identify small molecule inhibitors for DRAK2, we performed a high throughput screening campaign using in-house chemical library and identified indirubin-3'-monoximes as novel class of DRAK2 inhibitors. Among the compounds tested, compound 16 exhibited the most potent inhibitory activity against DRAK2 (IC50 = 0.003 mu M). We also propose that compound 16 may bind to the ATP-binding site of the enzyme based on enzyme kinetics and molecular docking studies. (C) 2016 Elsevier Ltd. All rights reserved.