Biochem Pharmacol:前列腺癌中代谢稳定的二苯胺衍生物能够抑制雄激素受体和BET蛋白

2020-04-11 AlexYang MedSci原创

雄激素受体(AR)是前列腺癌(PC)的一种关键的驱使因子。目前,AR相关的抗性仍旧是去势抵抗性前列腺癌(CRPC)治疗的重大挑战。溴域和末端外结构域(BET)家族是AR的关键共调控因子。

雄激素受体(AR)是前列腺癌(PC)的一种关键的驱使因子。目前,AR相关的抗性仍旧是去势抵抗性前列腺癌(CRPC)治疗的重大挑战。溴域和末端外结构域(BET)家族是AR的关键共调控因子。

最近,有研究人员开发了几种二苯胺衍生物,并鉴定了化合物7d能够干扰前列腺癌中AR和BET家族的功能,并表现出了良好的体外试验代谢稳定性和体内试验中较高的药物接触。研究人员阐释了7d不仅能够结合到AR,抑制正常AR(wt-AR)和突变体AR的反式激活(该反式激活能够介导恩杂鲁胺抗性),同时也能够通过抑制BET减少c-Myc蛋白的表达。另外,7d能够选择性的抑制AR阳性PC细胞的增殖,以及抑制AR-V7表达VCaP和22Rv1异种种植模型在体内的生长。

最后,研究人员指出,他们的结果表明了先导化合物7d具有成为口服AR和BET抑制剂药物来治疗CRPC和克服抗性激素抗性的可能性。

原始出处:

Yu J, Zhou P, Du W et al. Metabolically stable diphenylamine derivatives suppress androgen receptor and BET protein in prostate cancer. Biochem Pharmacol. 02 Apri 2020

 

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createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Sat Aug 01 06:39:49 CST 2020, time=2020-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1350568, encodeId=84711350568eb, content=<a href='/topic/show?id=a7689869104' target=_blank style='color:#2F92EE;'>#雄激素受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98691, encryptionId=a7689869104, topicName=雄激素受体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Mon Apr 13 05:39:49 CST 2020, time=2020-04-13, status=1, ipAttribution=)]
    2021-03-15 huirong
  5. 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  6. 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createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Sat Aug 01 06:39:49 CST 2020, time=2020-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1350568, encodeId=84711350568eb, content=<a href='/topic/show?id=a7689869104' target=_blank style='color:#2F92EE;'>#雄激素受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98691, encryptionId=a7689869104, topicName=雄激素受体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Mon Apr 13 05:39:49 CST 2020, time=2020-04-13, status=1, ipAttribution=)]
    2020-11-07 jj000001
  7. 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createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Sat Aug 01 06:39:49 CST 2020, time=2020-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1350568, encodeId=84711350568eb, content=<a href='/topic/show?id=a7689869104' target=_blank style='color:#2F92EE;'>#雄激素受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98691, encryptionId=a7689869104, topicName=雄激素受体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Mon Apr 13 05:39:49 CST 2020, time=2020-04-13, status=1, ipAttribution=)]
    2020-12-25 sunylz
  8. 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  9. 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    2020-08-01 yb6560
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