identificationstructuremodificationandcharacterizationofpotentialsmallmoleculesgk3inhibitorswithnovelscaffolds
文献类型：期刊论文
| 作者 | Grace Qun Gong1; Ke Wang4; XinChuan Dai1; Yan Zhou1; Rajesh Basnet1; Yi Chen1 ; DeHua Yang1; WooJeong Lee2; Christina Maree Buchanan2; Jack Urquhart Flanagan3
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| 刊名 | 中国药理学报英文版
 |
| 出版日期 | 2018 |
| 卷号 | 039期号:012页码:1902 |
| 关键词 | serum and glucocorticoid-regulated kinase SGK3 high-throughput screening inhibitors molecular modeling |
| ISSN号 | 1671-4083 |
| 英文摘要 | The serum and glucocorticoid-regulated kinase (SGK) family has been implicated in the regulation of many cellular processes downstream of the PI3K pathway. It plays a crucial role in PI3K-mediated tumorigenesis, making it a potential therapeutic target for cancer. SGK family consists of three isoforms (SGK1, SGK2, and SGK3), which have high sequence homology in the kinase domain and similar substrate speci?city with the AKT family. In order to identify novel compounds capable of inhibiting SGK3 activity, a high-throughput screening campaign against 50,400 small molecules was conducted using a fuorescence-based kinase assay that has a Z' factor above 0.5. It identiifed 15 hits (including nitrogen-containing aromatic, favone, hydrazone, and naphthalene derivatives) with IC50 values in the low micromolar to sub-micromolar range. Four compounds with a similar scaffold (i.e., a hydrazone core) were selected for structural modi?cation and 18 derivatives were synthesized. Molecular modeling was then used to investigate the structure-activity relationship (SAR) and potential protein–ligand interactions. As a result, a series of SGK inhibitors that are active against both SGK1 and SGK3 were developed and important functional groups that control their inhibitory activity identified. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/284718]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences (CAS 2.Department of Molecular Medicine and Pathology,The University of Auckland,Auckland,New Zealand 3.The Maurice Wilkins Centre,Auckland,New Zealand 4.School of Pharmacy,Fudan University 5.中国科学院大学 6.Auckland Cancer Society Research Centre,Auckland,New Zealand |
| 推荐引用方式 GB/T 7714 | Grace Qun Gong,Ke Wang,XinChuan Dai,et al. identificationstructuremodificationandcharacterizationofpotentialsmallmoleculesgk3inhibitorswithnovelscaffolds[J]. 中国药理学报英文版,2018,039(012):1902. |
| APA | Grace Qun Gong.,Ke Wang.,XinChuan Dai.,Yan Zhou.,Rajesh Basnet.,...&MingWei Wang.(2018).identificationstructuremodificationandcharacterizationofpotentialsmallmoleculesgk3inhibitorswithnovelscaffolds.中国药理学报英文版,039(012),1902. |
| MLA | Grace Qun Gong,et al."identificationstructuremodificationandcharacterizationofpotentialsmallmoleculesgk3inhibitorswithnovelscaffolds".中国药理学报英文版 039.012(2018):1902. |
入库方式： OAI收割
来源：上海药物研究所
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