國家衛生研究院 NHRI:Item 3990099045/8815
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    题名: Discovery of ATR kinase inhibitors from natural products
    作者: Wang, HC;Lee, AYL;Wu, CC;Wu, YC
    贡献者: National Institute of Cancer Research
    摘要: Inhibition of the DNA damage checkpoint and repair functions is a promising approach to improve chemosensitivity. Ataxia telangiectasia and Rad3-related protein (ATR) is an important checkpoint kianse responsible for organizing both normal and stressful DNA replication. In previous, we discovered a natural compound protoapigenone (WYC02) and its synthetic derivate WYC0209 are able to inhibit ATR-mediated Chk1 phosphorylation, impair the G2/M checkpoint, and improve cancer sensitivity to cisplatin both in vitro and in vivo. Although all evidences convince ATR signaling is disrupted by WYC compounds, the effect of compounds on ATR kinase activity is still unknown. In this study, we further provide evidences to prove that WYC02 and WYC0209 are undoubted ATR inhibitors by using of in vitro kinase assay. The data showed WYC0209 inhibits ATR kinase activity at least 4 times greater than WYC02, and enhances MDA-MB-231cells sensitivity to DNA replication-affecting agents such as doxorubicin, mitomycin C, and etoposide, but has little or no effect to mitosis-affecting microtubule inhibitor palcitaxol. The result of this study proposes a strategy to improve most of current chemotherapeutics in which aim to selective disrupting DNA replication in fast growing cancers.
    日期: 2014-10
    關聯: Cancer Research. 2014 Oct;74(19 Suppl.):Abstract No. 1637.
    Link to: http://dx.doi.org/10.1158/1538-7445.am2014-1637
    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:000349906901359
    显示于类别:[李岳倫] 會議論文/會議摘要

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