Blood：FF-10101，一种新型FLT3抑制剂，为携带FLT3突变的AML患者带来新的希望。

2017-12-06 MedSci MedSci原创

FLT3激活性突变，是与急性粒细胞白血病（AML）预后不良相关的最常见的遗传突变。尽管现临床上已经研发了多种FLT3抑制剂，但由于药物代谢差或低选择性、安全性差，尚无一种一代抑制剂在单药治疗中表现出临床疗效。近期，一种选择性FLT3抑制剂，quizartinib，在临床研究中证实效果良好。然而，在疾病的进展过程中出现了几种耐药性突变。为克服这些问题，Takeshi Yamaura等人研发了一种新型

FLT3激活性突变，是与急性粒细胞白血病（AML）预后不良相关的最常见的遗传突变。尽管现临床上已经研发了多种FLT3抑制剂，但由于药物代谢差或低选择性、安全性差，尚无一种一代抑制剂在单药治疗中表现出临床疗效。

近期，一种选择性FLT3抑制剂，quizartinib，在临床研究中证实效果良好。然而，在疾病的进展过程中出现了几种耐药性突变。

为克服这些问题，Takeshi Yamaura等人研发了一种新型FLT3抑制剂，FF-10101，一种选择性的不可逆性的FLT3抑制剂。

FLT3蛋白的共晶结构与FF-10101结合，提示FF-10101与FLT3的第695位的半胱氨酸残基形成共价结合。该特异性结合使FF-10101具有高度的选择性和抑制FLT3激酶的活性。FF-10101对携带各种突变的（TLT3-ITD、MOLM-13、MV4-11）人类AML细胞系以及所检测到的所有FLT3表达的突变32D细胞（FLT3激酶域的D835、Y842和F691残基上发生的对quizartinib有耐药性的突变）表现出强效的生长抑制的效果。

利用皮下移植瘤小鼠发现，口服FF-10101对FLT3-ITD-D835Y-/FLT3-ITD-F691L-表达32D细胞有显著的生长抑制的效果。

而且，FF-10101还可有效的抑制携带FLT30ITD或FLT3-D835突变的体内外AML原始细胞生长。

综上所述，FF-10101极有可能可用于治疗携带FLT3突变的AML患者，包括临床上确认的quizartinib耐药的突变。

原始出处：

Takeshi Yamaura，et al.A novel irreversible FLT3 inhibitor， FF-10101， shows excellent efficacy against AML cells with FLT3 mutations.Blood 2017 ：blood-2017-05-786657； doi： https：//doi.org/10.1182/blood-2017-05-786657

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2017-12-21 jklm09

#抑制剂#

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2017-12-08 fengyi816

#FLT3#

31 0
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2017-12-08 szhvet

#FLT3抑制剂#

36 0
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channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Dec 07 06:00:24 CST 2017, time=2017-12-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=267406, encodeId=01aa26e40682, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Thu Dec 07 05:32:32 CST 2017, time=2017-12-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=267396, encodeId=aacb26e39639, content=谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 07 00:55:09 CST 2017, time=2017-12-07, status=1, ipAttribution=)]
2017-12-07 大叔默默路过

不错的分享.谢谢

62 0
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channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Dec 07 06:00:24 CST 2017, time=2017-12-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=267406, encodeId=01aa26e40682, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Thu Dec 07 05:32:32 CST 2017, time=2017-12-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=267396, encodeId=aacb26e39639, content=谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 07 00:55:09 CST 2017, time=2017-12-07, status=1, ipAttribution=)]
2017-12-07 榄枷檬

学习学习

52 0
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objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 07 00:55:09 CST 2017, time=2017-12-07, status=1, ipAttribution=)]
2017-12-07 执着追梦

学习.谢谢分享

61 0
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objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 07 00:55:09 CST 2017, time=2017-12-07, status=1, ipAttribution=)]
2017-12-07 深海的鱼

学习吧.现在

60 0
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objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 07 00:55:09 CST 2017, time=2017-12-07, status=1, ipAttribution=)]
2017-12-07 刘煜

谢谢分享.阅读

56 0
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objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 07 00:55:09 CST 2017, time=2017-12-07, status=1, ipAttribution=)]
2017-12-07 yjs木玉

好好好好好好好好

26 0
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2017-12-07 天地飞扬

谢谢分享!

28 0