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Cell Res:去泛素化酶家族特异性抑制剂开发新靶点

2018-09-29 BioArt BioArt

去泛素化酶家族特异性抑制剂开发新靶点
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泛素化/去泛素化是一种动态的蛋白质双向修饰调控系统，在体内由泛素连接酶（E1-E2-E3）和去泛素化酶（DUB）家族分别负责。与磷酸化/去磷酸化系统类似，通过参与细胞内众多信号通路，泛素化双向修饰决定了很多生理事件的发生发展，被认为是极具潜力的癌症及神经类等疾病的治疗新靶点。

泛素化/去泛素化是一种动态的蛋白质双向修饰调控系统，在体内由泛素连接酶（E1-E2-E3）和去泛素化酶（DUB）家族分别负责。与磷酸化/去磷酸化系统类似，通过参与细胞内众多信号通路，泛素化双向修饰决定了很多生理事件的发生发展，被认为是极具潜力的癌症及神经类等疾病的治疗新靶点。

去泛素化酶（DUB）通过去除蛋白质底物上的泛素链，影响蛋白质的命运。其中，Ubiquitin Specific Proteinase（USP）家族，是数量最多的一类去泛素化酶亚家族。同蛋白激酶类似，由于USP家族成员活性中心空间结构高度相似，USP的选择性抑制剂发现面临巨大挑战。2010年，哈佛大学医学院Finley和King首次在Nature上报道了一种小分子IU1，其对前列腺癌、乳腺癌、结肠癌的重要潜在靶点USP14的抑制活性明显优于其他去泛素化酶，显示了其对USP14的高度选择性。但是由于缺乏结构生物学数据，IU1对USP14的选择性抑制机制尚不清楚，严重阻碍了高活性小分子的进一步优化，本项研究依此展开。

9月25日，中国农业科学院生物技术研究所梅子青课题组、清华大学生命科学学院王佳伟课题组、清华大学药学院何伟课题组以及北京理工大学生命学院王丰课题组在Cell Research杂志发表题为“Small molecule inhibitors reveal allosteric regulation of USP14 via steric blockade”的论文，揭示小分子化合物IU1选择性抑制去泛素化酶USP14的分子机制， 并基于结构优化出活性增加10倍的小分子IU1-248。

在这项研究中，研究人员通过解析去泛素化酶USP14催化结构域（CAT）和IU1复合物的原子分辨率晶体结构（1.96？），本研究揭示了IU1与USP14特异性结合模式。通过系列生物化学与生物物理学实验，验证了IU1是通过空间阻滞的别构调节方式选择性抑制USP14。令人惊讶的是，USP14CAT-IU1结构与先前报道的USP7及其抑制剂的复合物结构比对结果显示，IU1这种调节方式和USP7别构抑制剂发挥作用机制极为类似。

左图：USP14CAT-IU1与USP14CAT-Ubal结构比对。右图：结构比对中放大IU1结合位置，可以发现IU1结合在距离酶活中心8.3？的位置，通过阻挡底物泛素C末端进入USP14酶活中心来发挥功能。

总的来说，本研究同USP7相关研究一同，对于进一步优化DUB靶向小分子、开发新药用于癌症的治疗具有重要意义，对发现其他去泛素化酶的抑制剂研究有重要的参考价值。

原始出处：
Wang Y1, Jiang Y2, Ding S3, et al.Small molecule inhibitors reveal allosteric regulation of USP14 via steric blockade.Cell Res. 2018 Sep 25. doi: 10.1038/s41422-018-0091-x. [Epub ahead of print]

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    2019-07-08 jklm09

    #抑制剂#

    0

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    2019-06-23 zhaozhouchifen

    #Cell#

    0

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    2019-02-20 ms8435843352634314

    #特异性抑制剂#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1851805, encodeId=8a391851805fb, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Jul 08 18:43:00 CST 2019, time=2019-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870888, encodeId=e4b818e0888c0, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jun 23 02:43:00 CST 2019, time=2019-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1798044, encodeId=54251e98044dd, content=<a href='/topic/show?id=c1ba6e95292' target=_blank style='color:#2F92EE;'>#特异性抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67952, encryptionId=c1ba6e95292, topicName=特异性抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqPdWFricgmt6Dde2ptNxJzD6Y9c4cxpXdTo4pNlVPARAnFdKu6nWIPele9icxApTaFgibq0uVlgRiceQ/132, createdBy=4b8c2500026, createdName=ms8435843352634314, createdTime=Wed Feb 20 02:43:00 CST 2019, time=2019-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961159, encodeId=2203196115999, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Jan 25 09:43:00 CST 2019, time=2019-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899241, encodeId=fa1a189924104, content=<a href='/topic/show?id=6f746e94170' target=_blank style='color:#2F92EE;'>#特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67941, encryptionId=6f746e94170, topicName=特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Wed Dec 26 23:43:00 CST 2018, time=2018-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352924, encodeId=d91d35292497, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Sun Nov 18 08:31:52 CST 2018, time=2018-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288262, encodeId=14ce1288262af, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575352, encodeId=a85215e53522f, content=<a href='/topic/show?id=26d83e25254' target=_blank style='color:#2F92EE;'>#去泛素化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37252, encryptionId=26d83e25254, topicName=去泛素化酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eb2c16117221, createdName=mashirong, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=347272, encodeId=6b6a34e27210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Sat Sep 29 21:55:02 CST 2018, time=2018-09-29, status=1, ipAttribution=)]
    2019-01-25 维他命

    #CEL#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1851805, encodeId=8a391851805fb, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Jul 08 18:43:00 CST 2019, time=2019-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870888, encodeId=e4b818e0888c0, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jun 23 02:43:00 CST 2019, time=2019-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1798044, encodeId=54251e98044dd, content=<a href='/topic/show?id=c1ba6e95292' target=_blank style='color:#2F92EE;'>#特异性抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67952, encryptionId=c1ba6e95292, topicName=特异性抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqPdWFricgmt6Dde2ptNxJzD6Y9c4cxpXdTo4pNlVPARAnFdKu6nWIPele9icxApTaFgibq0uVlgRiceQ/132, createdBy=4b8c2500026, createdName=ms8435843352634314, createdTime=Wed Feb 20 02:43:00 CST 2019, time=2019-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961159, encodeId=2203196115999, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Jan 25 09:43:00 CST 2019, time=2019-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899241, encodeId=fa1a189924104, content=<a href='/topic/show?id=6f746e94170' target=_blank style='color:#2F92EE;'>#特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67941, encryptionId=6f746e94170, topicName=特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Wed Dec 26 23:43:00 CST 2018, time=2018-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352924, encodeId=d91d35292497, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Sun Nov 18 08:31:52 CST 2018, time=2018-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288262, encodeId=14ce1288262af, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575352, encodeId=a85215e53522f, content=<a href='/topic/show?id=26d83e25254' target=_blank style='color:#2F92EE;'>#去泛素化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37252, encryptionId=26d83e25254, topicName=去泛素化酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eb2c16117221, createdName=mashirong, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=347272, encodeId=6b6a34e27210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Sat Sep 29 21:55:02 CST 2018, time=2018-09-29, status=1, ipAttribution=)]
    2018-12-26 jinweidong

    #特异性#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1851805, encodeId=8a391851805fb, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Jul 08 18:43:00 CST 2019, time=2019-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870888, encodeId=e4b818e0888c0, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jun 23 02:43:00 CST 2019, time=2019-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1798044, encodeId=54251e98044dd, content=<a href='/topic/show?id=c1ba6e95292' target=_blank style='color:#2F92EE;'>#特异性抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67952, encryptionId=c1ba6e95292, topicName=特异性抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqPdWFricgmt6Dde2ptNxJzD6Y9c4cxpXdTo4pNlVPARAnFdKu6nWIPele9icxApTaFgibq0uVlgRiceQ/132, createdBy=4b8c2500026, createdName=ms8435843352634314, createdTime=Wed Feb 20 02:43:00 CST 2019, time=2019-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961159, encodeId=2203196115999, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Jan 25 09:43:00 CST 2019, time=2019-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899241, encodeId=fa1a189924104, content=<a href='/topic/show?id=6f746e94170' target=_blank style='color:#2F92EE;'>#特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67941, encryptionId=6f746e94170, topicName=特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Wed Dec 26 23:43:00 CST 2018, time=2018-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352924, encodeId=d91d35292497, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Sun Nov 18 08:31:52 CST 2018, time=2018-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288262, encodeId=14ce1288262af, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575352, encodeId=a85215e53522f, content=<a href='/topic/show?id=26d83e25254' target=_blank style='color:#2F92EE;'>#去泛素化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37252, encryptionId=26d83e25254, topicName=去泛素化酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eb2c16117221, createdName=mashirong, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=347272, encodeId=6b6a34e27210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Sat Sep 29 21:55:02 CST 2018, time=2018-09-29, status=1, ipAttribution=)]
    2018-11-18 kafei

    学习了谢谢

    0

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    2018-10-01 一叶知秋

    #新靶点#

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1851805, encodeId=8a391851805fb, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Jul 08 18:43:00 CST 2019, time=2019-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870888, encodeId=e4b818e0888c0, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jun 23 02:43:00 CST 2019, time=2019-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1798044, encodeId=54251e98044dd, content=<a href='/topic/show?id=c1ba6e95292' target=_blank style='color:#2F92EE;'>#特异性抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67952, encryptionId=c1ba6e95292, topicName=特异性抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqPdWFricgmt6Dde2ptNxJzD6Y9c4cxpXdTo4pNlVPARAnFdKu6nWIPele9icxApTaFgibq0uVlgRiceQ/132, createdBy=4b8c2500026, createdName=ms8435843352634314, createdTime=Wed Feb 20 02:43:00 CST 2019, time=2019-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961159, encodeId=2203196115999, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Jan 25 09:43:00 CST 2019, time=2019-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899241, encodeId=fa1a189924104, content=<a href='/topic/show?id=6f746e94170' target=_blank style='color:#2F92EE;'>#特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67941, encryptionId=6f746e94170, topicName=特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Wed Dec 26 23:43:00 CST 2018, time=2018-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352924, encodeId=d91d35292497, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Sun Nov 18 08:31:52 CST 2018, time=2018-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288262, encodeId=14ce1288262af, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575352, encodeId=a85215e53522f, content=<a href='/topic/show?id=26d83e25254' target=_blank style='color:#2F92EE;'>#去泛素化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37252, encryptionId=26d83e25254, topicName=去泛素化酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eb2c16117221, createdName=mashirong, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=347272, encodeId=6b6a34e27210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Sat Sep 29 21:55:02 CST 2018, time=2018-09-29, status=1, ipAttribution=)]
    2018-10-01 mashirong

    #去泛素化酶#

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1851805, encodeId=8a391851805fb, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Jul 08 18:43:00 CST 2019, time=2019-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870888, encodeId=e4b818e0888c0, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jun 23 02:43:00 CST 2019, time=2019-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1798044, encodeId=54251e98044dd, content=<a href='/topic/show?id=c1ba6e95292' target=_blank style='color:#2F92EE;'>#特异性抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67952, encryptionId=c1ba6e95292, topicName=特异性抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqPdWFricgmt6Dde2ptNxJzD6Y9c4cxpXdTo4pNlVPARAnFdKu6nWIPele9icxApTaFgibq0uVlgRiceQ/132, createdBy=4b8c2500026, createdName=ms8435843352634314, createdTime=Wed Feb 20 02:43:00 CST 2019, time=2019-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961159, encodeId=2203196115999, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Jan 25 09:43:00 CST 2019, time=2019-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899241, encodeId=fa1a189924104, content=<a href='/topic/show?id=6f746e94170' target=_blank style='color:#2F92EE;'>#特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67941, encryptionId=6f746e94170, topicName=特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Wed Dec 26 23:43:00 CST 2018, time=2018-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352924, encodeId=d91d35292497, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Sun Nov 18 08:31:52 CST 2018, time=2018-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288262, encodeId=14ce1288262af, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575352, encodeId=a85215e53522f, content=<a href='/topic/show?id=26d83e25254' target=_blank style='color:#2F92EE;'>#去泛素化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37252, encryptionId=26d83e25254, topicName=去泛素化酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eb2c16117221, createdName=mashirong, createdTime=Mon Oct 01 12:43:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=347272, encodeId=6b6a34e27210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Sat Sep 29 21:55:02 CST 2018, time=2018-09-29, status=1, ipAttribution=)]
    2018-09-29 医者仁心5538

    学习了

    0