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Sci Rep：一种基于色酮的STAT3抑制剂Erasin，在厄洛替尼耐药的肺癌细胞中诱导凋亡

2017-12-29 xiangting MedSci原创

肺癌厄洛替尼STAT3Erasin
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这项研究验证了基于色酮的酰腙是拮抗STAT SH2结构域的优势结构。

小分子抑制蛋白质-蛋白质间的相互作用给基础研究和药物开发提供了巨大的机会。这个研究领域面临的根本挑战之一是普遍缺乏天然可用的引线结构。这项研究证明了对转录因子STAT5的Src同源性2（SH2）结构域的基于色酮的抑制剂进行修饰，可以赋予针对STAT3的抑制活性。通过化学合成和生化活性分析以及分子对接研究，结构-活性关系研究分析了最有效的STAT3抑制剂Erasin的结合方式。在基于细胞的测定中，Erasin选择性抑制STAT3的酪氨酸磷酸化，而不是STAT5和STAT1，并以STAT3依赖的方式增加培养的NSCLC细胞的凋亡率。Erasin的这种能力也延伸到获得性厄洛替尼耐药的HCC-827细胞，厄洛替尼是临床上使用的EGF受体抑制剂。

这项研究验证了基于色酮的酰腙是拮抗STAT SH2结构域的优势结构，并且证明可以通过直接抑制STAT3在获得性厄洛替尼耐药的NSCLC细胞中诱导细胞凋亡。

原始出处：

本文系梅斯医学(MedSci)原创编译整理，转载需授权！

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    2018-02-13 jklm09

    #抑制剂#

    0

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    2018-05-27 kalseyzl

    #肺癌细胞#

    0

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    2018-03-02 124988c7m106暂无昵称

    #ERA#

    0

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    2018-04-17 1249862am72(暂无昵称)

    #RASI#

    0

  5. 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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Fri Dec 29 19:38:56 CST 2017, time=2017-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=273550, encodeId=dd5f2e3550d9, content=小分子抑制蛋白质-蛋白质间的相互作用给基础研究和药物开发提供了巨大的机会.这个研究领域面临的根本挑战之一是普遍缺乏天然可用的引线结构, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Fri Dec 29 17:03:43 CST 2017, time=2017-12-29, status=1, ipAttribution=)]
    2018-04-10 ms1260584454294838

    #Erasin#

    0

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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Fri Dec 29 19:38:56 CST 2017, time=2017-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=273550, encodeId=dd5f2e3550d9, content=小分子抑制蛋白质-蛋白质间的相互作用给基础研究和药物开发提供了巨大的机会.这个研究领域面临的根本挑战之一是普遍缺乏天然可用的引线结构, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Fri Dec 29 17:03:43 CST 2017, time=2017-12-29, status=1, ipAttribution=)]
    2017-12-31 yxch36

    #癌细胞#

    0

  7. 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    2017-12-31 ms306040998833292

    #厄洛替尼#

    0

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    2017-12-31 李研东

    #STAT3#

    0

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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Fri Dec 29 19:38:56 CST 2017, time=2017-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=273550, encodeId=dd5f2e3550d9, content=小分子抑制蛋白质-蛋白质间的相互作用给基础研究和药物开发提供了巨大的机会.这个研究领域面临的根本挑战之一是普遍缺乏天然可用的引线结构, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Fri Dec 29 17:03:43 CST 2017, time=2017-12-29, status=1, ipAttribution=)]
    2017-12-29 131****1460

    学习了受益匪浅

    0

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    2017-12-29 有备才能无患

    小分子抑制蛋白质-蛋白质间的相互作用给基础研究和药物开发提供了巨大的机会.这个研究领域面临的根本挑战之一是普遍缺乏天然可用的引线结构

    0

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