國家衛生研究院 NHRI:Item 3990099045/12289
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    题名: An Aurora kinase inhibitor BPR6K471 inhibits tumor growth and reduces the cancer stem cell-like properties of small cell lung cancer
    作者: Chang, CP;Ke, YY;Lin, WH;Jhuo, DH;Wang, WP;Tsai, CH;Chen, YT;Su, YJ;Hung, MC;Wu, ZW;Kuo, PC;Yeh, TK;Chen, CP;Song, JS;Chen, CT;Shih, C;Chi, YH
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: Small cell lung cancer (SCLC) is one the most aggressive tumors with poor survival rate. SCLC patients often present with metastasis at time of diagnosis, excluding surgery as a treatment option. While patients show high response rate to standard chemotherapy such as cisplatin/etoposide, they soon develop drug resistance and disease progression. Therefore, new therapeutic strategies are urgently needed for SCLC. Several characteristics of SCLC such as aggressiveness and drug resistance could attribute to the existence of a cancer stem cell (CSC) subpopulation in SCLC. The SCLC cell line NCI-H446 has been shown to present high degree of stemness and express stem cell markers including CD133, OCT4, MYC and Nestin. Here we develop a pyrimidine-based small molecule BPR6K471 which potently inhibits Aurora kinase activities in enzymatic- and cell- based assays. BPR6K471 efficiently (IC50 = 66 nM) inhibits proliferation of NCI-H446, and reduces the expression of stem-cell markers. In addition, intravenous injection of BPR6K471 inhibits >90 % progression of NCI-H446 in a mouse xenograft model. These results suggest that targeting Aurora kinases may be a potential therapeutic strategy to combat the CSC subpopulation in SCLC.
    日期: 2019-07
    關聯: Cancer Research. 2019 Jul;79(13, Suppl.):Abstract number 3851.
    Link to: http://dx.doi.org/10.1158/1538-7445.Am2019-3851
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000488279403250
    显示于类别:[紀雅惠] 會議論文/會議摘要
    [石全(2014-2017)] 會議論文/會議摘要
    [陳炯東] 會議論文/會議摘要
    [葉燈光] 會議論文/會議摘要
    [張竣評] 會議論文/會議摘要

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