Design, synthesis and pharmacological evaluation of 4,5-diarylisoxazols bearing amino acid residues within the 3-amido motif as potent heat shock protein 90 (Hsp90) inhibitors
文献类型：期刊论文
| 作者 | Zhang, Chi1,3; Wang, Xin2,4 ; Liu, Hongchun2; Zhang, Minmin2; Geng, Meiyu2; Sun, Liping1; Shen, Aijun2; Zhang, Ao3
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2017-01-05 |
| 卷号 | 125页码:315-326 |
| 关键词 | Diarylisoxazole Resorcinol Amino acid Hsp90 inhibitor Antiproliferative effect |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2016.09.043 |
| 文献子类 | Article |
| 英文摘要 | A structure-based medicinal chemistry optimization was conducted on the clinical Hsp90 inhibitor diarylisoxazole 3. Several series of new compounds were designed and synthesized by incorporating diversified amino acid derivatives with various lengths to the 3-amido motif of the isoxazole scaffold. Compound 14j was identified to have high Hsp90 binding potency (14 nM) and antiproliferative activity against H3122 human lung cancer and BT-474 breast cancer cells. Treatment of 14j with H3122 cell led to degradation of client protein ALK, reduction of downstream phosphorylation of AKT and ERK, and up regulation of Hsp70. Molecular docking suggested that the terminal valine moiety and the ethyleneglycol linker in compound 14j formed additional apolar and polar interaction network with a number of amino acid residues. (C) 2016 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | TYROSINE KINASE INHIBITORS ; ADVANCED SOLID TUMORS ; CANCER CELL-LINES ; I DOSE-ESCALATION ; CHAPERONE INHIBITORS ; MOLECULAR CHAPERONES ; ANTICANCER AGENTS ; SANSALVAMIDE ; AUY922 ; DERIVATIVES |
| 资助项目 | Chinese National Science Foundation[81430080] ; Shanghai Commission of Science and Technology[14431905300] ; Shanghai Commission of Science and Technology[16XD1404600] ; Shanghai Institute of Materia Medica[CASIMM0120154002/2002] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000390496600023 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275683]  |
| 专题 | 药理学第一研究室 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 | Sun, Liping; Shen, Aijun; Zhang, Ao |
| 作者单位 | 1.China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, SIMM, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, CAS Key Lab Receptor Res, Synthet Organ & Med Chem Lab, SIMM, Shanghai 201203, Peoples R China; 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Chi,Wang, Xin,Liu, Hongchun,et al. Design, synthesis and pharmacological evaluation of 4,5-diarylisoxazols bearing amino acid residues within the 3-amido motif as potent heat shock protein 90 (Hsp90) inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,125:315-326. |
| APA | Zhang, Chi.,Wang, Xin.,Liu, Hongchun.,Zhang, Minmin.,Geng, Meiyu.,...&Zhang, Ao.(2017).Design, synthesis and pharmacological evaluation of 4,5-diarylisoxazols bearing amino acid residues within the 3-amido motif as potent heat shock protein 90 (Hsp90) inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,125,315-326. |
| MLA | Zhang, Chi,et al."Design, synthesis and pharmacological evaluation of 4,5-diarylisoxazols bearing amino acid residues within the 3-amido motif as potent heat shock protein 90 (Hsp90) inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 125(2017):315-326. |
入库方式： OAI收割
来源：上海药物研究所
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