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AI-10-49

现货
Catalog No.
A8694
CBFβ-SMMHC和RUNX1相互作用的抑制剂。
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,200.00
现货
5mg
¥ 800.00
现货
10mg
¥ 1,400.00
现货
25mg
¥ 2,800.00
Ship with 10-15 days

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Background

AI-10-49 is a selective inhibitor of CBFβ –SMMHC and RUNX1 interaction with a FRET IC50 value of 260nM.
AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient with AI-10-49 triggers selective cell death. Direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers. The stability of RUNX1, CBFb, and CBFb-SMMHC was not affected by AI-10-49 [1].
In 11 human leukemia cell lines, ME-1 cells were the only cell line highly sensitive to AI-10-49. In ME-1 cell, AI-10-49 has enhanced inhibitory activity on growth (IC50 = 0.6 mM) compared with the parent protonated bivalent compound AI-4-83 (IC50 of ~3 mM). In normal human bone marrow cells, AI-10-49 showed negligible activity (IC50 > 25 mM), which indicated a robust potential therapeutic window. In chromatin-immunoprecipitation (ChIP) assays, treatment of ME-1 cells for 6 hours with AI-10-49 increased RUNX1 occupancy 8-, 2.2-, and 8-fold at the RUNX3, CSF1R, and CEBPA promoters, respectively.
After treatment with AI-10-49 to leukemia mice significantly prolonged their lives, and after 7 days of administration of AI-10-49, we observe no evidence of toxicity [1].
Reference:
1.Illendula A, Pulikkan JA, Zong H et al. A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice. Science. 2015 Feb 13;347(6223):779-784.

Chemical Properties

StorageStore at -20°C
M.Wt660.52
Cas No.1256094-72-0
FormulaC30H22F6N6O5
Solubility≥16.53mg/mL in DMSO
Chemical Name2,2'-(5,5'-((oxybis(ethane-2,1-diyl))bis(oxy))bis(pyridine-5,2-diyl))bis(5-(trifluoromethoxy)-1H-benzo[d]imidazole)
SDFDownload SDF
Canonical SMILESFC(F)(F)OC1=CC2=C(C=C1)NC(C(C=C3)=NC=C3OCCOCCOC(C=C4)=CN=C4C5=NC6=CC(OC(F)(F)F)=CC=C6N5)=N2
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

ME-1人白血病细胞系

制备方法

溶解度有限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

6 h

实验结果

在处理6小时后,AI-10-49有效地将RUNX1从CBFb-SMMHC中解离90%,相比之下,它对CBFb-RUNX1结合的影响较为温和。ChIP实验表明,使用AI-10-49处理ME-1细胞6小时将RUNX3、CSF1R和CEBPA启动子处RUNX1的占据率分别增加8倍、2.2倍和8倍。

动物实验: [1]

动物模型

Cbfb +/MYH11:Ras +/G12D白血病细胞移植小鼠

给药剂量

200 mg/kg,10天

实验结果

AI-10-49处理的小鼠存活时间明显延长,平均延迟61天,并且瞬时AI-10-49治疗也减少体内白血病扩散。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

1. Illendula A, Pulikkan JA, Zong H et.al A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice. Science. 2015 Feb 13;347(6223):779-84.

质量控制

质量控制和MSDS

批次:

化学结构

AI-10-49