Identification and optimization of novel 6-acylamino-2-aminoquinolines as potent Hsp90 C-terminal inhibitors
Identification and optimization of novel 6-acylamino-2-aminoquinolines as potent Hsp90 C-terminal inhibitors
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新型 6-酰氨基-2-氨基喹啉作为有效 Hsp90 C 末端抑制剂的鉴定和优化。
DOI：
10.1016/j.ejmech.2017.07.080
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发表时间：
2017-12-01
影响因子：
6.7
通讯作者：
Xu, Xiao-li
中科院分区：
文献类型：
--
作者：
Jiang, Fen;Guo, An-ping;Xu, Xiao-li
为了发现针对c端ATP结合袋的新型Hsp90抑制剂，构建了基于新生物素衍生物的ROCS模型进行虚拟筛选。以化合物13为先导化合物，进行了系统构效关系（SAR）研究。这些努力导致化合物69对MCF7和SKBr3乳腺癌细胞系表现出有效的抗增殖活性。在4T1小鼠乳腺癌模型中，69只小鼠表现出明显的肿瘤生长抑制和抗转移作用。化合物69作为一种有效的靶向Hsp90 c末端的抗肿瘤药物，值得进一步的临床前研究。(C) 2017年由Elsevier Masson SAS出版。
In order to discover novel Hsp90 inhibitors targeting the C-terminal ATP binding pocket, a novobiocin derivative based ROCS model was constructed for virtual screening. Compound 13 was identified as the lead compound and then systematical structure activity relationship (SAR) study was conducted. These efforts led to compound 69, which exhibited potent anti-proliferative activities against MCF7 and SKBr3 breast cancer cell lines. In 4T1 mice breast cancer models, 69 exhibited potent tumor growth inhibition and anti-metastasis effect. Compound 69 as a potent antitumor agent targeting the Hsp90 C-terminal is worthy of further pre-clinical study. (C) 2017 Published by Elsevier Masson SAS.