非酒精性脂肪性肝炎(NASH)迎来新进展:lanifibranor达到期中研究的主要终点

2020-06-16 Allan MedSci原创

随着肥胖及其相关代谢综合征全球化的流行趋势,非酒精性脂肪性肝病现已成为欧美等发达国家和我国富裕地区慢性肝病的重要病因。

随着肥胖及其相关代谢综合征全球化的流行趋势,非酒精性脂肪性肝病现已成为欧美等发达国家和我国富裕地区慢性肝病的重要病因。制药公司Inventiva报道称,在一项IIb期试验中,实验性药物lanifibranor治疗非酒精性脂肪性肝炎(NASH)达到了主要终点以及主要次要终点。该公司表示,根据这些数据,它计划将小分子泛PPAR激动剂lanifibranor推进到III期临床中。

IIb期试验(NATIVE研究)的结果表明,与基线相比,接受高剂量lanifibranor的患者的脂肪变性纤维化(SAF)评分至少降低了至少两个点。具体而言,lanifibranor高剂量组中有49%的患者达到了主要终点,而安慰剂组为27%。该公司补充说,两种剂量的lanifibranor均达到了主要次要终点,且不会使纤维化恶化。

Inventiva首席科学官Pierre Broqua表示:“鉴于这是一项全球性试验,lanifibranor在仅仅六个月的治疗中就同时达到了FDA和EMA监管指标。因此我们对候选药物lanifibranor在III期关键性临床试验中的潜力感到乐观”。

不过,去年泛PPAR激动剂Lanifibranor在一个叫做FASST的全身性硬化病二期临床IIb失败这个实验招募145位弥漫性皮肤全身性硬化病("dcSSc")患者比较一日两次400600毫克两个剂量Lanifibranor安慰剂对一个叫做mRSS皮肤指数的改善结果在标准疗法背景上用药48周三组患者无差异该试验也错过所有二级终点。

PPAR是一类核受体,因为调控脂代谢直接影响线粒体功能和氧化应激,所以被认为与纤维化有关。但每个亚型的PPAR都控制大量功能不同基因,同时激活所有PPAR是个风险很大的策略。PPARgama激动剂如Avandia、Actos曾是最大的一类糖尿病药物,但2007年Avandia被拉下神坛、并导致FDA增加了对所有糖尿病、减肥药物的心血管安全性数据强制要求。虽然后来Avandia平反昭雪、最近FDA也准备放宽对糖尿病药物安全性要求,但是PPAR的复杂性给业界上了一课。在Avandia出事之前很多大公司在开发PPARalpha/gama双激动剂,但心衰、出血等严重副作用令这些药物先后失败。即使PPARgama激动剂后来也有人研究说并非通过PPAR起效,而是通过CDK5。

PPAR显然是一类表达广泛、功能繁多的靶点,虽然与脂代谢、炎症、纤维化有关,但是找到有足够安全窗口而不影响其它功能的药物虽然不是不可能但也是一个技术难题。这类高度复杂靶点需要非常严格、准确的评价系统才能找到有足够安全窗口的药物,但现在纤维化疾病的临床前评价体系尚不完善。盲人骑瞎马,这样寻找高回报的代价是高风险。Lanifibranor据说已经优化到没有Avandia类似物的副作用、今天这个临床安全性也不错,但是因为副作用担心没有使用足够剂量也是一个难以排除的因素。药理相对简单的elafibrinor在NASH二期临床信号也非常微弱,但仍挺进三期、RESOLVE-IT试验今年即会有结果。希望Lanifibranor在NASH的运气更好一点

原始出处:

https://www.firstwordpharma.com/node/1732942?tsid=4

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content=<a href='/topic/show?id=397299e19c7' target=_blank style='color:#2F92EE;'>#非酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99719, encryptionId=397299e19c7, topicName=非酒精性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon Sep 14 05:07:33 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956092, encodeId=6dfb195609253, content=<a href='/topic/show?id=8a048435058' target=_blank style='color:#2F92EE;'>#脂肪性肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84350, encryptionId=8a048435058, topicName=脂肪性肝炎)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Jr8S1dfvNyP22t32IFDXJXnpd5AGlDibiajL5cl3pxj7OPCeAeibLhzOmZn5Q2Oicc6uKOCnxGNOggdLtI3hIW7huQ/132, createdBy=66e52500008, createdName=Tamikia, createdTime=Tue Jan 26 07:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1301308, encodeId=3754130130890, content=<a href='/topic/show?id=38e32852fe' target=_blank style='color:#2F92EE;'>#ASH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2852, encryptionId=38e32852fe, topicName=ASH)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=39a0295, createdName=kksonne, createdTime=Thu Jun 18 12:07:33 CST 2020, time=2020-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602439, encodeId=3f94602439a0, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>PPAR显然是一类表达广泛、功能繁多的靶点,3期仍然高风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:36:05 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602438, encodeId=f523602438de, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>研发领域的第二个大坑,都期待突破。第一个坑是AD, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:35:18 CST 2020, time=2020-06-17, status=1, ipAttribution=)]
    2021-01-26 qjddjq
  4. [GetPortalCommentsPageByObjectIdResponse(id=1673584, encodeId=af6516e358440, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=398f26933958, createdName=huiwelcome, createdTime=Mon Jan 25 15:07:33 CST 2021, time=2021-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950970, encodeId=104a9509e07b, content=<a href='/topic/show?id=3d2b99e2119' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99721, encryptionId=3d2b99e2119, topicName=非酒精性脂肪性肝)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Thu Mar 25 11:55:11 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1810174, encodeId=d15d18101e4a2, content=<a href='/topic/show?id=70f484349b5' target=_blank style='color:#2F92EE;'>#脂肪性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84349, encryptionId=70f484349b5, topicName=脂肪性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Tue Jan 26 16:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996976, encodeId=9dcf19969e687, content=<a href='/topic/show?id=b706232e831' target=_blank style='color:#2F92EE;'>#主要终点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23278, encryptionId=b706232e831, topicName=主要终点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7387164, createdName=zhangj7108, createdTime=Tue Jun 30 01:07:33 CST 2020, time=2020-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991214, encodeId=7fad199121454, content=<a href='/topic/show?id=7b0299e238b' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝炎(NASH)#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99723, encryptionId=7b0299e238b, topicName=非酒精性脂肪性肝炎(NASH))], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=56ea361, createdName=changhe713, createdTime=Tue Oct 27 08:07:33 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676567, encodeId=ae9316e656760, content=<a href='/topic/show?id=397299e19c7' target=_blank style='color:#2F92EE;'>#非酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99719, encryptionId=397299e19c7, topicName=非酒精性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon Sep 14 05:07:33 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956092, encodeId=6dfb195609253, content=<a href='/topic/show?id=8a048435058' target=_blank style='color:#2F92EE;'>#脂肪性肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84350, encryptionId=8a048435058, topicName=脂肪性肝炎)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Jr8S1dfvNyP22t32IFDXJXnpd5AGlDibiajL5cl3pxj7OPCeAeibLhzOmZn5Q2Oicc6uKOCnxGNOggdLtI3hIW7huQ/132, createdBy=66e52500008, createdName=Tamikia, createdTime=Tue Jan 26 07:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1301308, encodeId=3754130130890, content=<a href='/topic/show?id=38e32852fe' target=_blank style='color:#2F92EE;'>#ASH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2852, encryptionId=38e32852fe, topicName=ASH)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=39a0295, createdName=kksonne, createdTime=Thu Jun 18 12:07:33 CST 2020, time=2020-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602439, encodeId=3f94602439a0, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>PPAR显然是一类表达广泛、功能繁多的靶点,3期仍然高风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:36:05 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602438, encodeId=f523602438de, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>研发领域的第二个大坑,都期待突破。第一个坑是AD, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:35:18 CST 2020, time=2020-06-17, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1673584, encodeId=af6516e358440, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=398f26933958, createdName=huiwelcome, createdTime=Mon Jan 25 15:07:33 CST 2021, time=2021-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950970, encodeId=104a9509e07b, content=<a href='/topic/show?id=3d2b99e2119' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99721, encryptionId=3d2b99e2119, topicName=非酒精性脂肪性肝)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Thu Mar 25 11:55:11 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1810174, encodeId=d15d18101e4a2, content=<a href='/topic/show?id=70f484349b5' target=_blank style='color:#2F92EE;'>#脂肪性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84349, encryptionId=70f484349b5, topicName=脂肪性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Tue Jan 26 16:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996976, encodeId=9dcf19969e687, content=<a href='/topic/show?id=b706232e831' target=_blank style='color:#2F92EE;'>#主要终点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23278, encryptionId=b706232e831, topicName=主要终点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7387164, createdName=zhangj7108, createdTime=Tue Jun 30 01:07:33 CST 2020, time=2020-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991214, encodeId=7fad199121454, content=<a href='/topic/show?id=7b0299e238b' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝炎(NASH)#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99723, encryptionId=7b0299e238b, topicName=非酒精性脂肪性肝炎(NASH))], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=56ea361, createdName=changhe713, createdTime=Tue Oct 27 08:07:33 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676567, encodeId=ae9316e656760, content=<a href='/topic/show?id=397299e19c7' target=_blank style='color:#2F92EE;'>#非酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99719, encryptionId=397299e19c7, topicName=非酒精性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon Sep 14 05:07:33 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956092, encodeId=6dfb195609253, content=<a href='/topic/show?id=8a048435058' target=_blank style='color:#2F92EE;'>#脂肪性肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84350, encryptionId=8a048435058, topicName=脂肪性肝炎)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Jr8S1dfvNyP22t32IFDXJXnpd5AGlDibiajL5cl3pxj7OPCeAeibLhzOmZn5Q2Oicc6uKOCnxGNOggdLtI3hIW7huQ/132, createdBy=66e52500008, createdName=Tamikia, createdTime=Tue Jan 26 07:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1301308, encodeId=3754130130890, content=<a href='/topic/show?id=38e32852fe' target=_blank style='color:#2F92EE;'>#ASH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2852, encryptionId=38e32852fe, topicName=ASH)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=39a0295, createdName=kksonne, createdTime=Thu Jun 18 12:07:33 CST 2020, time=2020-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602439, encodeId=3f94602439a0, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>PPAR显然是一类表达广泛、功能繁多的靶点,3期仍然高风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:36:05 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602438, encodeId=f523602438de, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>研发领域的第二个大坑,都期待突破。第一个坑是AD, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:35:18 CST 2020, time=2020-06-17, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1673584, encodeId=af6516e358440, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=398f26933958, createdName=huiwelcome, createdTime=Mon Jan 25 15:07:33 CST 2021, time=2021-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950970, encodeId=104a9509e07b, content=<a href='/topic/show?id=3d2b99e2119' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99721, encryptionId=3d2b99e2119, topicName=非酒精性脂肪性肝)], attachment=null, authenticateStatus=null, 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channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23278, encryptionId=b706232e831, topicName=主要终点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7387164, createdName=zhangj7108, createdTime=Tue Jun 30 01:07:33 CST 2020, time=2020-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991214, encodeId=7fad199121454, content=<a href='/topic/show?id=7b0299e238b' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝炎(NASH)#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99723, encryptionId=7b0299e238b, topicName=非酒精性脂肪性肝炎(NASH))], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=56ea361, createdName=changhe713, createdTime=Tue Oct 27 08:07:33 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676567, encodeId=ae9316e656760, content=<a href='/topic/show?id=397299e19c7' target=_blank style='color:#2F92EE;'>#非酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99719, encryptionId=397299e19c7, topicName=非酒精性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon Sep 14 05:07:33 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956092, encodeId=6dfb195609253, content=<a href='/topic/show?id=8a048435058' target=_blank style='color:#2F92EE;'>#脂肪性肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84350, encryptionId=8a048435058, topicName=脂肪性肝炎)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Jr8S1dfvNyP22t32IFDXJXnpd5AGlDibiajL5cl3pxj7OPCeAeibLhzOmZn5Q2Oicc6uKOCnxGNOggdLtI3hIW7huQ/132, createdBy=66e52500008, createdName=Tamikia, createdTime=Tue Jan 26 07:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1301308, encodeId=3754130130890, content=<a href='/topic/show?id=38e32852fe' target=_blank style='color:#2F92EE;'>#ASH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2852, encryptionId=38e32852fe, topicName=ASH)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=39a0295, createdName=kksonne, createdTime=Thu Jun 18 12:07:33 CST 2020, time=2020-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602439, encodeId=3f94602439a0, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>PPAR显然是一类表达广泛、功能繁多的靶点,3期仍然高风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:36:05 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602438, encodeId=f523602438de, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>研发领域的第二个大坑,都期待突破。第一个坑是AD, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:35:18 CST 2020, time=2020-06-17, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1673584, encodeId=af6516e358440, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=398f26933958, createdName=huiwelcome, createdTime=Mon Jan 25 15:07:33 CST 2021, time=2021-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950970, encodeId=104a9509e07b, content=<a href='/topic/show?id=3d2b99e2119' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99721, encryptionId=3d2b99e2119, topicName=非酒精性脂肪性肝)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Thu Mar 25 11:55:11 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1810174, encodeId=d15d18101e4a2, content=<a href='/topic/show?id=70f484349b5' target=_blank style='color:#2F92EE;'>#脂肪性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84349, encryptionId=70f484349b5, topicName=脂肪性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Tue Jan 26 16:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996976, encodeId=9dcf19969e687, content=<a href='/topic/show?id=b706232e831' target=_blank style='color:#2F92EE;'>#主要终点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23278, encryptionId=b706232e831, topicName=主要终点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7387164, createdName=zhangj7108, createdTime=Tue Jun 30 01:07:33 CST 2020, time=2020-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991214, encodeId=7fad199121454, content=<a href='/topic/show?id=7b0299e238b' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝炎(NASH)#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99723, encryptionId=7b0299e238b, topicName=非酒精性脂肪性肝炎(NASH))], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=56ea361, createdName=changhe713, createdTime=Tue Oct 27 08:07:33 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676567, encodeId=ae9316e656760, content=<a href='/topic/show?id=397299e19c7' target=_blank style='color:#2F92EE;'>#非酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99719, encryptionId=397299e19c7, topicName=非酒精性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon Sep 14 05:07:33 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956092, encodeId=6dfb195609253, content=<a href='/topic/show?id=8a048435058' target=_blank style='color:#2F92EE;'>#脂肪性肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84350, encryptionId=8a048435058, topicName=脂肪性肝炎)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Jr8S1dfvNyP22t32IFDXJXnpd5AGlDibiajL5cl3pxj7OPCeAeibLhzOmZn5Q2Oicc6uKOCnxGNOggdLtI3hIW7huQ/132, createdBy=66e52500008, createdName=Tamikia, createdTime=Tue Jan 26 07:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1301308, encodeId=3754130130890, content=<a href='/topic/show?id=38e32852fe' target=_blank style='color:#2F92EE;'>#ASH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2852, encryptionId=38e32852fe, topicName=ASH)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=39a0295, createdName=kksonne, createdTime=Thu Jun 18 12:07:33 CST 2020, time=2020-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602439, encodeId=3f94602439a0, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>PPAR显然是一类表达广泛、功能繁多的靶点,3期仍然高风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:36:05 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602438, encodeId=f523602438de, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>研发领域的第二个大坑,都期待突破。第一个坑是AD, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:35:18 CST 2020, time=2020-06-17, status=1, ipAttribution=)]
  8. 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createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Thu Mar 25 11:55:11 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1810174, encodeId=d15d18101e4a2, content=<a href='/topic/show?id=70f484349b5' target=_blank style='color:#2F92EE;'>#脂肪性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84349, encryptionId=70f484349b5, topicName=脂肪性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Tue Jan 26 16:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996976, encodeId=9dcf19969e687, content=<a href='/topic/show?id=b706232e831' target=_blank style='color:#2F92EE;'>#主要终点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23278, encryptionId=b706232e831, topicName=主要终点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7387164, createdName=zhangj7108, createdTime=Tue Jun 30 01:07:33 CST 2020, time=2020-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991214, encodeId=7fad199121454, content=<a href='/topic/show?id=7b0299e238b' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝炎(NASH)#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99723, encryptionId=7b0299e238b, topicName=非酒精性脂肪性肝炎(NASH))], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=56ea361, createdName=changhe713, createdTime=Tue Oct 27 08:07:33 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676567, encodeId=ae9316e656760, content=<a href='/topic/show?id=397299e19c7' target=_blank style='color:#2F92EE;'>#非酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99719, encryptionId=397299e19c7, topicName=非酒精性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon Sep 14 05:07:33 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956092, encodeId=6dfb195609253, content=<a href='/topic/show?id=8a048435058' target=_blank style='color:#2F92EE;'>#脂肪性肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84350, encryptionId=8a048435058, topicName=脂肪性肝炎)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Jr8S1dfvNyP22t32IFDXJXnpd5AGlDibiajL5cl3pxj7OPCeAeibLhzOmZn5Q2Oicc6uKOCnxGNOggdLtI3hIW7huQ/132, createdBy=66e52500008, createdName=Tamikia, createdTime=Tue Jan 26 07:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1301308, encodeId=3754130130890, content=<a href='/topic/show?id=38e32852fe' target=_blank style='color:#2F92EE;'>#ASH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2852, encryptionId=38e32852fe, topicName=ASH)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=39a0295, createdName=kksonne, createdTime=Thu Jun 18 12:07:33 CST 2020, time=2020-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602439, encodeId=3f94602439a0, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>PPAR显然是一类表达广泛、功能繁多的靶点,3期仍然高风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:36:05 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602438, encodeId=f523602438de, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>研发领域的第二个大坑,都期待突破。第一个坑是AD, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:35:18 CST 2020, time=2020-06-17, status=1, ipAttribution=)]
    2020-06-18 kksonne
  9. 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content=<a href='/topic/show?id=397299e19c7' target=_blank style='color:#2F92EE;'>#非酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99719, encryptionId=397299e19c7, topicName=非酒精性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon Sep 14 05:07:33 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956092, encodeId=6dfb195609253, content=<a href='/topic/show?id=8a048435058' target=_blank style='color:#2F92EE;'>#脂肪性肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84350, encryptionId=8a048435058, topicName=脂肪性肝炎)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Jr8S1dfvNyP22t32IFDXJXnpd5AGlDibiajL5cl3pxj7OPCeAeibLhzOmZn5Q2Oicc6uKOCnxGNOggdLtI3hIW7huQ/132, createdBy=66e52500008, createdName=Tamikia, createdTime=Tue Jan 26 07:07:33 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1301308, encodeId=3754130130890, content=<a href='/topic/show?id=38e32852fe' target=_blank style='color:#2F92EE;'>#ASH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2852, encryptionId=38e32852fe, topicName=ASH)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=39a0295, createdName=kksonne, createdTime=Thu Jun 18 12:07:33 CST 2020, time=2020-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602439, encodeId=3f94602439a0, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>PPAR显然是一类表达广泛、功能繁多的靶点,3期仍然高风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:36:05 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602438, encodeId=f523602438de, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>研发领域的第二个大坑,都期待突破。第一个坑是AD, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:35:18 CST 2020, time=2020-06-17, status=1, ipAttribution=)]
    2020-06-17 lovetcm

    #NASH#PPAR显然是一类表达广泛、功能繁多的靶点,3期仍然高风险

    0

  10. 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style='color:#2F92EE;'>#NASH#</a>PPAR显然是一类表达广泛、功能繁多的靶点,3期仍然高风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Jun 17 20:36:05 CST 2020, time=2020-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=602438, encodeId=f523602438de, content=<a href='/topic/show?id=04ea125266c' target=_blank style='color:#2F92EE;'>#NASH#</a>研发领域的第二个大坑,都期待突破。第一个坑是AD, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12526, encryptionId=04ea125266c, topicName=NASH)], attachment=null, authenticateStatus=null, 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    2020-06-17 lovetcm

    #NASH#研发领域的第二个大坑,都期待突破。第一个坑是AD

    0

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