标题:Structural optimization elaborates novel potent Akt inhibitors with promising anticancer activity
作者:Liu, Yang; Yin, Yanzhen; Zhang, Zhen; Li, Carrie J.; Zhang, Hui; Zhang, Daoguang; Jiang, Changying; Nomie, Krystle; Zhang, Liang; Wa 更多
作者机构:[Liu, Yang; Yin, Yanzhen; Zhang, Zhen; Zhang, Daoguang; Zhao, Guisen] Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 更多
通讯作者:Zhao, GS;Wang, ML
通讯作者地址:[Zhao, GS]Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, Jinan 250012, Shandong, Peoples R China;[Wang, ML]Univ Texa 更多
来源:EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版年:2017
卷:138
页码:543-551
DOI:10.1016/j.ejmech.2017.06.067
关键词:Akt; Anticancer; Docking; Mantle cell lymphoma; Piperidyl;; Pyrrolopyrimidines
摘要:Targeting of Akt has been validated as a well rationalized approach to cancer treatment, and represents a promising therapeutic strategy for aggressive hematologic malignancies. We describe herein an exploration of novel Akt inhibitors for cancer therapy through structural optimization of previously described 4-(piperazin-1-yI)-7H-pyrrolo[2,3-dlpyrimidine derivatives. Our studies yielded a novel series of pyrrolopyrimidine based phenylpiperidine carboxamides capable of potent inhibition of Aktl. Notably, 10h exhibited robust antiproliferative effects in both mantle cell lymphoma cell lines and primary patient tumor cells. Low micromolar doses of 10h induced cell apoptosis and cell cycle arrest in G(2)/M phase, and significantly downregulated the phosphorylation of Akt downstream effectors GSI3 beta and S6 in Jeko-1 cells. (C) 2017 Elsevier Masson SAS. All rights reserved.
收录类别:SCOPUS;SCIE
Scopus被引频次:2
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021884164&doi=10.1016%2fj.ejmech.2017.06.067&partnerID=40&md5=bf3daa9952866365d347207abfe41b05
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