Profile of the GSK published protein kinase inhibitor set across ATP-dependent and-independent luciferases: implications for reporter-gene assays.
Profile of the GSK published protein kinase inhibitor set across ATP-dependent and-independent luciferases: implications for reporter-gene assays.
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DOI：
10.1371/journal.pone.0057888
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Inglese J
中科院分区：
文献类型：
--
作者：
Dranchak P;MacArthur R;Guha R;Zuercher WJ;Drewry DH;Auld DS;Inglese J
A library of 367 protein kinase inhibitors, the GSK Published Kinase Inhibitor Set (PKIS), which has been annotated for protein kinase family activity and is available for public screening efforts, was assigned against the commonly used luciferase reporter enzymes from the firefly, Phototinus pyralis （FLUC）和海洋三色菜，Renilla Reniformis（RLUC），共有22种化合物（约6％的文库）抑制了10种化合物，显示了两种化合物≤1µm。这些显示相对较弱的效能值（约10 µm）。化学型抑制剂对酪氨酸激酶和CDK家族具有广泛的活性。例如使用正交记者鉴定激酶或非激酶介导的细胞反应。
A library of 367 protein kinase inhibitors, the GSK Published Kinase Inhibitor Set (PKIS), which has been annotated for protein kinase family activity and is available for public screening efforts, was assayed against the commonly used luciferase reporter enzymes from the firefly, Photinus pyralis (FLuc) and marine sea pansy, Renilla reniformis (RLuc). A total of 22 compounds (∼6% of the library) were found to inhibit FLuc with 10 compounds showing potencies ≤1 µM. Only two compounds were found to inhibit RLuc, and these showed relatively weak potency values (∼10 µM). An inhibitor series of the VEGFR2/TIE2 protein kinase family containing either an aryl oxazole or benzimidazole-urea core illustrate the different structure activity relationship profiles FLuc inhibitors can display for kinase inhibitor chemotypes. Several FLuc inhibitors were broadly active toward the tyrosine kinase and CDK families. These data should aid in interpreting the results derived from screens employing the GSK PKIS in cell-based assays using the FLuc reporter. The study also underscores the general need for strategies such as the use of orthogonal reporters to identify kinase or non-kinase mediated cellular responses.
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