Design, synthesis and biological evaluation of pyrazol-furan carboxamide analogues as novel Akt kinase inhibitors
文献类型：期刊论文
| 作者 | Zhan, Wenhu2; Xu, Lei1; Dong, Xiaowu2; Dong, Jun2; Yi, Xiao2; Ma, Xiaodong2; Qiu, Ni2; Li, Jia1 ; Yang, Bo2; Zhou, Yubo1
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2016-07-19 |
| 卷号 | 117页码:47-58 |
| 关键词 | Akt1 inhibitor Synthesis Cytotoxicity Molecular docking Cancer |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2016.03.074 |
| 文献子类 | Article |
| 英文摘要 | A series of novel pyrazol-furan carboxamide analogues were designed, synthesized and biologically evaluated for their Akt1 inhibitory activities, as well as anti -proliferative efficacies against HCT116 and OVCAR-8 cell lines. Most compounds exhibited moderate to excellent Akt1 inhibitory activities, together with favorable cytotoxicities. Further kinase selectivity assay of the most promising compound 25e illustrated that it was also potent against the structurally related AGC kinases, including Akt2, Akt3, ROCK1 and PICA, but was specific over kinases from other subfamilies. In addition, the Western blot analysis indicated that 25e could significantly suppress the phosphorylation level of Akt substrate GSK3 beta in PC-3 cell. Moreover, 25e demonstrated a concentration-dependent inhibition of phosphorylation of PRAS40 in LNCaP cell, with IC50 value of 30.4 nM. (C) 2016 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | SHOWS FAVORABLE SAFETY ; PRECLINICAL PHARMACOLOGY ; ANTITUMOR-ACTIVITY ; CLINICAL ACTIVITY ; MULTIPLE-MYELOMA ; CANCER CELLS ; PHASE-I ; DISCOVERY ; PATHWAY ; AFURESERTIB |
| 资助项目 | Zhejiang province Provincial Natural Science Foundation of China[LY13H300002] ; Program for Zhejiang Leading Team of ST Innovation[2011R50014] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000376837800005 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275953]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 |
| 通讯作者 | Zhou, Yubo; Hu, Yongzhou |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 2.Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Zhejiang, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhan, Wenhu,Xu, Lei,Dong, Xiaowu,et al. Design, synthesis and biological evaluation of pyrazol-furan carboxamide analogues as novel Akt kinase inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2016,117:47-58. |
| APA | Zhan, Wenhu.,Xu, Lei.,Dong, Xiaowu.,Dong, Jun.,Yi, Xiao.,...&Hu, Yongzhou.(2016).Design, synthesis and biological evaluation of pyrazol-furan carboxamide analogues as novel Akt kinase inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,117,47-58. |
| MLA | Zhan, Wenhu,et al."Design, synthesis and biological evaluation of pyrazol-furan carboxamide analogues as novel Akt kinase inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 117(2016):47-58. |
入库方式： OAI收割
来源：上海药物研究所
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