Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: Development of chemical probe ML315
Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: Development of chemical probe ML315
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DOI：
10.1016/j.bmcl.2013.02.096
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发表时间：
2013-06-15
影响因子：
2.7
通讯作者：
Aube, Jeffrey
中科院分区：
文献类型：
--
作者：
Coombs, Thomas C.;Tanega, Cordelle;Aube, Jeffrey
已开发Clk和Dyrk激酶的取代嘧啶抑制剂，探索围绕四种不同化学型的结构-活性关系。最有效的化合物对Clk 1、Clk 2、Clk 4、Dyrk 1A和Dyrk 1B具有低纳摩尔抑制活性。使用代表三种化学型的试剂用442种激酶进行的激酶组扫描显示这些抑制剂对Clk和Dyrk家族具有高度选择性。ML 315（最具选择性的药物）的进一步脱靶药理学评价支持这一结论。(C)2013爱思唯尔有限公司保留所有权利。
Substituted pyrimidine inhibitors of the Clk and Dyrk kinases have been developed, exploring structure-activity relationships around four different chemotypes. The most potent compounds have low-nanomolar inhibitory activity against Clk1, Clk2, Clk4, Dyrk1A and Dyrk1B. Kinome scans with 442 kinases using agents representing three of the chemotypes show these inhibitors to be highly selective for the Clk and Dyrk families. Further off-target pharmacological evaluation with ML315, the most selective agent, supports this conclusion. (C) 2013 Elsevier Ltd. All rights reserved.