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DMH-1

现货
Catalog No.
B3686
BMP ALK2受体抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 900.00
现货
10mg
¥ 800.00
现货
25mg
¥ 1,600.00
现货
50mg
¥ 2,400.00
现货

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Background

DMH1 is a small molecule inhibitor of bone morphogenetic protein (BMP) signaling with IC50 value of 107.9nM against ALK2 [1].

DMH1 is an analog of dorsomorphin. It exclusively targets BMP and has no effect on VEGF signaling. DMH1 shows potent and specific inhibitory activity against purified human BMP type-I receptor ALK2 with IC50 value of 107.9nM. It shows no significant inhibition of purified KDR, ALK5, AMPK and PDGFRβ. In cells respectively transfected with the active forms of ALK2, ALK3 and ALK6, DMH1 effectively inhibits signaling by ALK2 and ALK3 with IC50 values of both less than 0.5μM. In addition, DMH1 has no effect on the p38/MAP kinase signaling or the Activin A-induced Smad2 activation [1].

Moreover, DMH1 is found to have antitumor effect in lung cancer through blocking BMP signaling. In the NSCLC cell line A549 cells, DMH1 inhibits the phosphorylation of Smad 1/5/8 and decreases the expression of Id1, Id2 and Id3 genes. It decreases cell migration and invasion in A549 and H460 cell line. Besides that, DMH1 reduces cell proliferation and induces cell death in A549 cells. In the A549 tumor xenograft in mice, treatment of DMH1significantly suppresses tumor growth [2].

References:
[1] Hao J, Ho J N, Lewis J A, et al. In vivo structure- activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. ACS chemical biology, 2010, 5(2): 245-253.
[2] Hao J, Lee R, Chang A, et al. DMH1, a Small Molecule Inhibitor of BMP Type I Receptors, Suppresses Growth and Invasion of Lung Cancer. PloS one, 2014, 9(3): e90748.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt380.44
Cas No.1206711-16-1
FormulaC24H20N4O
Solubility≥9.511mg/mL in DMSO
SDFDownload SDF
Canonical SMILESCC(C)OC1=CC=C(C=C1)C2=CN3C(=C(C=N3)C4=CC=NC5=CC=CC=C45)N=C2
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

激酶实验[1]:

抑制活性

DMH1是BMP I型受体的小分子抑制剂,在NSCLC细胞中,DMH1通过阻断BMP信号有效地减少肺细胞增殖,促进细胞死亡,并减少细胞迁移和侵袭。DMH1抑制Smad 1/5/8磷酸化和Id1、Id2以及Id3的基因表达。

细胞实验[1]:

细胞系

A549 和H460 细胞

制备方法

该化合物在DMSO中的溶解度大于10 mM,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

细胞刮伤试验:24小时,1 μM和3 μM浓度的DMH1。细胞增殖试验:孵育48小时和96小时

实验结果

DMH1阻断NSCLC细胞中的BMP信号传导并降低NSCLC细胞迁移和侵袭,DMH1减少NSCLC细胞增殖并诱导细胞死亡。

动物实验[1]:

动物模型

异种移植模型

给药剂量

5 mg/kg DMH1,每隔一天

制备方法

溶于12.5%2-羟丙基-β-环糊精

实验结果

在DMH1处理的小鼠中,肿瘤大小加倍的速率比对照长约一天,DMH1处理和对照小鼠中分别为5.6和4.7天。 与对照组相比,MH1导致肿瘤体积统计学显著减少约50%。总之,DMH1减少小鼠的异种移植肺肿瘤生长

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Jijun Hao, Rachel Lee, Andy Chang, et al. DMH1, a Small Molecule Inhibitor of BMP Type I Receptors, Suppresses Growth and Invasion of Lung Cancer. 2014, 9(3): e90748.

生物活性

描述 DMH1是一种选择性的BMP受体抑制剂,作用于ALK2,IC50值为107.9 nM。
靶点 BMP signaling ALK2        
IC50 100 nM 107.9 nM        

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