fDiscovery of pyrazole-thiophene derivatives as highly Potent, orally active Akt inhibitors
文献类型：期刊论文
| 作者 | Zhan, Wenhu2,4; Che, Jinxin2; Xu, Lei3; Wu, Yizhe2; Hu, Xiaobei3; Zhou, Yubo3 ; Cheng, Gang1; Hu, Yongzhou2; Dong, Xiaowu2; Li, Jia3
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2019-10-15 |
| 卷号 | 180页码:72-85 |
| 关键词 | Pyrazole-thiophene derivatives Akt inhibitor Antitumor |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2019.07.017 |
| 通讯作者 | Dong, Xiaowu(dongxw@zju.edu.cn) ; Li, Jia(jli@simm.ac.cn) |
| 英文摘要 | A series of pyrazole-thiophene derivatives exhibiting good Akt inhibitory activities were obtained on the basis of conformational restriction strategy, leading to the discovery of compound 1d and 1o which showed excellent in vitro antitumor effect against a variety of hematologic cancer cells and their potential of inducing apoptosis, blocking the cell cycles at S phase and significantly inhibiting the phosphorylation of downstream biomarkers of Akt kinase of cancer cells. Amongst, compound 1o also exhibited good PK profiles and inhibited about 40% tumor growth in MM1S xenograft model. Compound 1o might be a potential candidate for further development. (C) 2019 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | BIOLOGICAL EVALUATION ; MOLECULAR DOCKING ; PATHWAY ; CANCER ; DESIGN ; ACTIVATION ; DISCOVERY ; AZD5363 |
| 资助项目 | National Natural Science Foundation of China ; National Major Scientific and Technological Special Project for Significant New Drugs Development |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000488307100007 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/282651]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Dong, Xiaowu; Li, Jia |
| 作者单位 | 1.Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou 311402, Zhejiang, Peoples R China 2.Zhejiang Univ, Hangzhou Inst Innovat Med, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem,Zhejiang Prov Key Lab, Hangzhou 310058, Zhejiang, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Weill Cornell Med, Dept Microbiol & Immunol, 1300 York Ave, New York, NY 10065 USA |
| 推荐引用方式 GB/T 7714 | Zhan, Wenhu,Che, Jinxin,Xu, Lei,et al. fDiscovery of pyrazole-thiophene derivatives as highly Potent, orally active Akt inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,180:72-85. |
| APA | Zhan, Wenhu.,Che, Jinxin.,Xu, Lei.,Wu, Yizhe.,Hu, Xiaobei.,...&Li, Jia.(2019).fDiscovery of pyrazole-thiophene derivatives as highly Potent, orally active Akt inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,180,72-85. |
| MLA | Zhan, Wenhu,et al."fDiscovery of pyrazole-thiophene derivatives as highly Potent, orally active Akt inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 180(2019):72-85. |
入库方式： OAI收割
来源：上海药物研究所
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