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综述：靶向蛋白降解(PROTACs)癌症治疗药物机制、以及新近进展、国内相关研发公司

2021-03-28 MedSci原创 MedSci原创

靶向蛋白降解
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靶向蛋白降解疗法是新药开发炙手可热的领域。去年，Arvinas公司蛋白降解剂（PROTAC）ARV-471和ARV-110的临床结果，让人们看到这一治疗模式在临床试验中的概念验证（详细见：Arvina

靶向蛋白降解疗法是新药开发炙手可热的领域。去年，Arvinas公司蛋白降解剂（PROTAC）ARV-471和ARV-110的临床结果，让人们看到这一治疗模式在临床试验中的概念验证（详细见：Arvinas宣布启动1期临床研究，评估其靶向雌激素受体的PROTAC蛋白质降解剂ARV-471治疗乳腺癌的活性）。 蛋白降解剂的探索与应用 不过在PROTAC之前，有一类蛋白降解药物已经获得FDA批准治疗多种血液癌症，只不过科学家们最近才发现它们抗癌的机理主要依靠降解与疾病相关的特定蛋白。这就是度胺类药物，包括沙利度胺（thalidomide）、来那度胺（lenalidomide）和泊马度胺（pomalidomide），但是这些药物靶向性不足。 蛋白降解药物的基本作用机制是利用泛素-蛋白酶体系统（UPS）来诱导特定蛋白的降解。E3泛素连接酶能够为需要降解的蛋白加上泛素标签，让它们被运送到蛋白酶体进行降解。人体中有超过600种E3泛素连接酶，而度胺类药物能够与其中最大的E3泛素连接酶家族Cullin–RING连接酶复合体中的CRBN蛋白结合，改变了CRBN蛋白与底物的结合特征，从而让新的底物蛋白被这一

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    2021-10-14 grace5700

    #TAC#

    0

  2. 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    2021-10-22 zhaozuguo

    #PROTACs#

    0

  3. 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    2022-01-13 陈吴1234

    #癌症治疗#

    0

  4. 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    2022-02-27 周虎

    #治疗药物#

    0

  5. 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    2021-03-31 ms5000000518166734

    已读，真是受益匪浅呀！

    0

  6. 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    2021-03-30 yaanren

    #ACS#

    0

  7. 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encryptionId=4f0a6469837, topicName=治疗药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9d3459, createdName=周虎, createdTime=Sun Feb 27 08:05:55 CST 2022, time=2022-02-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952617, encodeId=5e4f95261e9e, content=已读，真是受益匪浅呀！, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Wed Mar 31 13:01:56 CST 2021, time=2021-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1279360, encodeId=b07212e93600b, content=<a href='/topic/show?id=316d1882bc' target=_blank style='color:#2F92EE;'>#ACS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1882, encryptionId=316d1882bc, topicName=ACS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=102a153, createdName=yaanren, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1300460, encodeId=2fb41300460b7, content=<a href='/topic/show?id=ed5ee332423' target=_blank style='color:#2F92EE;'>#研发#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73324, encryptionId=ed5ee332423, topicName=研发)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aea0290, createdName=lqvr, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1602351, encodeId=ca05160235179, content=<a href='/topic/show?id=2f801469e57' target=_blank style='color:#2F92EE;'>#PRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14697, encryptionId=2f801469e57, topicName=PRO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a60b18898917, createdName=sunylz, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=951991, encodeId=6da1951991ad, content=<a href='/topic/show?id=aa0582e6946' target=_blank style='color:#2F92EE;'>#肿瘤#</a>这都是<a href='/topic/show?id=d8dbe130197' target=_blank style='color:#2F92EE;'>#癌症#</a>的创新药物，这篇总结得超好！！值得细细品读！, beContent=null, objectType=article, channel=null, level=null, likeNumber=440, replyNumber=1, topicName=null, topicId=null, topicList=[TopicDto(id=82769, encryptionId=aa0582e6946, topicName=肿瘤), TopicDto(id=71301, encryptionId=d8dbe130197, topicName=癌症)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Mon Mar 29 10:03:44 CST 2021, time=2021-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952051, encodeId=6f1c952051cc, content=关注进一步研究结果, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=579a5131299, createdName=14657eeam65(暂无昵称), createdTime=Mon Mar 29 15:05:23 CST 2021, time=2021-03-29, status=1, ipAttribution=)]
    2021-03-30 lqvr

    #研发#

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=2033736, encodeId=4e2b2033e3647, content=<a href='/topic/show?id=fc431e0708f' target=_blank style='color:#2F92EE;'>#TAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17070, encryptionId=fc431e0708f, topicName=TAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b05b180, createdName=grace5700, createdTime=Thu Oct 14 13:05:55 CST 2021, time=2021-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1791769, encodeId=7da01e91769b7, content=<a href='/topic/show?id=e78314e52c9' target=_blank style='color:#2F92EE;'>#PROTACs#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14752, encryptionId=e78314e52c9, topicName=PROTACs)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=263b421, createdName=zhaozuguo, createdTime=Fri Oct 22 14:05:55 CST 2021, time=2021-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1844309, encodeId=f4f7184430925, content=<a href='/topic/show?id=06a2e1405a8' target=_blank style='color:#2F92EE;'>#癌症治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71405, encryptionId=06a2e1405a8, topicName=癌症治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cbf451, createdName=陈吴1234, createdTime=Thu Jan 13 21:05:55 CST 2022, time=2022-01-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1921822, encodeId=c8f219218222f, content=<a href='/topic/show?id=4f0a6469837' target=_blank style='color:#2F92EE;'>#治疗药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64698, encryptionId=4f0a6469837, topicName=治疗药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9d3459, createdName=周虎, createdTime=Sun Feb 27 08:05:55 CST 2022, time=2022-02-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952617, encodeId=5e4f95261e9e, content=已读，真是受益匪浅呀！, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Wed Mar 31 13:01:56 CST 2021, time=2021-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1279360, encodeId=b07212e93600b, content=<a href='/topic/show?id=316d1882bc' target=_blank style='color:#2F92EE;'>#ACS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1882, encryptionId=316d1882bc, topicName=ACS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=102a153, createdName=yaanren, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1300460, encodeId=2fb41300460b7, content=<a href='/topic/show?id=ed5ee332423' target=_blank style='color:#2F92EE;'>#研发#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73324, encryptionId=ed5ee332423, topicName=研发)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aea0290, createdName=lqvr, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1602351, encodeId=ca05160235179, content=<a href='/topic/show?id=2f801469e57' target=_blank style='color:#2F92EE;'>#PRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14697, encryptionId=2f801469e57, topicName=PRO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a60b18898917, createdName=sunylz, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=951991, encodeId=6da1951991ad, content=<a href='/topic/show?id=aa0582e6946' target=_blank style='color:#2F92EE;'>#肿瘤#</a>这都是<a href='/topic/show?id=d8dbe130197' target=_blank style='color:#2F92EE;'>#癌症#</a>的创新药物，这篇总结得超好！！值得细细品读！, beContent=null, objectType=article, channel=null, level=null, likeNumber=440, replyNumber=1, topicName=null, topicId=null, topicList=[TopicDto(id=82769, encryptionId=aa0582e6946, topicName=肿瘤), TopicDto(id=71301, encryptionId=d8dbe130197, topicName=癌症)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Mon Mar 29 10:03:44 CST 2021, time=2021-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952051, encodeId=6f1c952051cc, content=关注进一步研究结果, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=579a5131299, createdName=14657eeam65(暂无昵称), createdTime=Mon Mar 29 15:05:23 CST 2021, time=2021-03-29, status=1, ipAttribution=)]
    2021-03-30 sunylz

    #PRO#

    0

  9. 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encryptionId=4f0a6469837, topicName=治疗药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9d3459, createdName=周虎, createdTime=Sun Feb 27 08:05:55 CST 2022, time=2022-02-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952617, encodeId=5e4f95261e9e, content=已读，真是受益匪浅呀！, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Wed Mar 31 13:01:56 CST 2021, time=2021-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1279360, encodeId=b07212e93600b, content=<a href='/topic/show?id=316d1882bc' target=_blank style='color:#2F92EE;'>#ACS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1882, encryptionId=316d1882bc, topicName=ACS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=102a153, createdName=yaanren, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1300460, encodeId=2fb41300460b7, content=<a href='/topic/show?id=ed5ee332423' target=_blank style='color:#2F92EE;'>#研发#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73324, encryptionId=ed5ee332423, topicName=研发)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aea0290, createdName=lqvr, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1602351, encodeId=ca05160235179, content=<a href='/topic/show?id=2f801469e57' target=_blank style='color:#2F92EE;'>#PRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14697, encryptionId=2f801469e57, topicName=PRO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a60b18898917, createdName=sunylz, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=951991, encodeId=6da1951991ad, content=<a href='/topic/show?id=aa0582e6946' target=_blank style='color:#2F92EE;'>#肿瘤#</a>这都是<a href='/topic/show?id=d8dbe130197' target=_blank style='color:#2F92EE;'>#癌症#</a>的创新药物，这篇总结得超好！！值得细细品读！, beContent=null, objectType=article, channel=null, level=null, likeNumber=440, replyNumber=1, topicName=null, topicId=null, topicList=[TopicDto(id=82769, encryptionId=aa0582e6946, topicName=肿瘤), TopicDto(id=71301, encryptionId=d8dbe130197, topicName=癌症)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Mon Mar 29 10:03:44 CST 2021, time=2021-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952051, encodeId=6f1c952051cc, content=关注进一步研究结果, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=579a5131299, createdName=14657eeam65(暂无昵称), createdTime=Mon Mar 29 15:05:23 CST 2021, time=2021-03-29, status=1, ipAttribution=)]
    2021-03-29 病毒猎手

    #肿瘤#这都是#癌症#的创新药物，这篇总结得超好！！值得细细品读！

    1

    展开1条回复
  10. [GetPortalCommentsPageByObjectIdResponse(id=2033736, encodeId=4e2b2033e3647, content=<a href='/topic/show?id=fc431e0708f' target=_blank style='color:#2F92EE;'>#TAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17070, encryptionId=fc431e0708f, topicName=TAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b05b180, createdName=grace5700, createdTime=Thu Oct 14 13:05:55 CST 2021, time=2021-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1791769, encodeId=7da01e91769b7, content=<a href='/topic/show?id=e78314e52c9' target=_blank style='color:#2F92EE;'>#PROTACs#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14752, encryptionId=e78314e52c9, topicName=PROTACs)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=263b421, 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encryptionId=4f0a6469837, topicName=治疗药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9d3459, createdName=周虎, createdTime=Sun Feb 27 08:05:55 CST 2022, time=2022-02-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952617, encodeId=5e4f95261e9e, content=已读，真是受益匪浅呀！, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Wed Mar 31 13:01:56 CST 2021, time=2021-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1279360, encodeId=b07212e93600b, content=<a href='/topic/show?id=316d1882bc' target=_blank style='color:#2F92EE;'>#ACS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1882, encryptionId=316d1882bc, topicName=ACS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=102a153, createdName=yaanren, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1300460, encodeId=2fb41300460b7, content=<a href='/topic/show?id=ed5ee332423' target=_blank style='color:#2F92EE;'>#研发#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73324, encryptionId=ed5ee332423, topicName=研发)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aea0290, createdName=lqvr, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1602351, encodeId=ca05160235179, content=<a href='/topic/show?id=2f801469e57' target=_blank style='color:#2F92EE;'>#PRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14697, encryptionId=2f801469e57, topicName=PRO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a60b18898917, createdName=sunylz, createdTime=Tue Mar 30 10:05:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=951991, encodeId=6da1951991ad, content=<a href='/topic/show?id=aa0582e6946' target=_blank style='color:#2F92EE;'>#肿瘤#</a>这都是<a href='/topic/show?id=d8dbe130197' target=_blank style='color:#2F92EE;'>#癌症#</a>的创新药物，这篇总结得超好！！值得细细品读！, beContent=null, objectType=article, channel=null, level=null, likeNumber=440, replyNumber=1, topicName=null, topicId=null, topicList=[TopicDto(id=82769, encryptionId=aa0582e6946, topicName=肿瘤), TopicDto(id=71301, encryptionId=d8dbe130197, topicName=癌症)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Mon Mar 29 10:03:44 CST 2021, time=2021-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952051, encodeId=6f1c952051cc, content=关注进一步研究结果, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=579a5131299, createdName=14657eeam65(暂无昵称), createdTime=Mon Mar 29 15:05:23 CST 2021, time=2021-03-29, status=1, ipAttribution=)]
    2021-03-29 14657eeam65(暂无昵称)

    关注进一步研究结果

    0

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