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Dorsomorphin 2HCl

现货
Catalog No.
B1372
AMPK抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
5mg
¥ 500.00
现货
10mg
¥ 750.00
现货
50mg
¥ 2,500.00
现货

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Background

IC50: Dorsomorphin inhibited BMP4-induced phosphorylation of BMP-responsive SMADs in a dose-dependent manner (half maximal inhibitory concentration (IC50) =0.47 mM).
Bone morphogenetic protein (BMP) signals coordinate developmental patterning and have essential physiological roles in mature organisms. The first known small-molecule inhibitor of BMP signaling, dorsomorphin, were identified in a screen for compounds that perturb dorsoventral axis formation in zebrafish.
In vitro: Previoius researchers found that dorsomorphin selectively inhibits the BMP type I receptors ALK2/ALK3/ALK6 leading to block BMP-mediated SMAD1/5/8 phosphorylation, osteogenic differentiation as well as target gene transcription. Using dorsomorphin, they examined the role of BMP signaling in iron homeostasis.dorsomorphin inhibited the systemic iron regulator hepcidin BMP-, hemojuvelin- and interleukin 6–stimulated expression, indicating that BMP receptors regulate hepcidin induction by all of these stimuli [1].
In vivo: The systemic challenge with iron rapidly induced SMAD1/5/8 phosphorylation and hepcidin expression in the liver, while dorsomorphin treatment could blocke SMAD1/5/8 phosphorylation, normalize hepcidin expression and increase serum iron levels. These suggest an crucial physiological role for hepatic BMP signaling in iron-hepcidin homeostasis [1].
Clinical trial: Dorsomorphin is still in preclinical development stage and no clinicl trial is ongoing currently.
Reference:
[1] Yu PB, Hong CC, Sachidanandan C, Babitt JL, Deng DY, Hoyng SA, Lin HY, Bloch KD, Peterson RT.Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2008;4(1):33-41.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt472.41
Cas No.1219168-18-9
FormulaC24H25N5O.2HCl
Solubility≥5.9mg/mL in DMSO, <3.76 mg/mL in EtOH, <6.74 mg/mL in H2O, ≥11.34 mg/mL in 0.9% NS
Chemical Name6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine;dihydrochloride
SDFDownload SDF
Canonical SMILESC1CCN(CC1)CCOC2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=CC=NC=C5)N=C3.Cl.Cl
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]:

AMPK 部分纯化和体外激酶试验。

将雄性SD大鼠的肝脏AMPK部分纯化,使其能够应用于蓝色琼脂糖凝胶步骤。100微升反应混合物包含100 μM AMP、100 μM ATP (0.5 μCi 33P-ATP 每个反应),和50 μM SAMS 缓冲液(40 mM HEPES、pH 7.0、80 mM NaCl、0.8 mM EDTA、5 mM MgCl2、0.025% BSA和0.8 mM DTT)。加入酶启动反应。在30℃下孵育30分钟后,加入80微升1% H3PO4停止反应。等分样品(100 μl)转移到96孔多层筛板。用1% H3PO4清洗板3次后,在Top-count上进行检测。体外AMPK抑制数据由化合物C-(6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine)-适用于竞争性抑制方程,即根据在Merck 研究实验室中N. Thornberry编写的电脑程序,Vi/Vo = (Km + S)/[S + Km × (1 + I/Ki)](其中Vi为抑制速率,Vo为初始速率,S是底物(ATP)浓度,Km是ATP的Michaelis常数,I是抑制剂(化合物 C)浓度,Ki是化合物C的解离常数) 用最小二乘法Marquardt算法通过非线性回归得到。

细胞实验 [2]:

细胞系

小鼠肺动脉平滑肌细胞、Hep3B 细胞

溶解方法

该化合物在DMSO中的溶解度有限。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。

反应时间

0.1-20 μM 处理30 min

应用

Dorsomorphin (4 μM)抑制C2C12细胞成骨分化并且通过干扰I型BMP受体功能机制抑制BMP介导的SMAD活化;同时Dorsomorphin (1 μM)处理肝癌衍生细胞,可干扰BMP及HJV介导的铁调节蛋白表达。

动物实验 [2]:

动物模型

斑马鱼胚胎模型; 野生型C57BL/6 成年鼠模型

剂量

10 mM dorsomorphin处理30 h; 或10 mg/ kg、腹腔注射给药

应用

Dorsomorphin诱导斑马鱼胚胎模型背部化;Dorsomorphin在体内模型中抑制骨矿化;除此之外,Dorsomorphin (10 mg/ kg) 在鼠模型中诱导高铁血症。

注意事项

请于室内测试所有化合物的溶解度。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. Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M. F., Goodyear, L. J. and Moller, D. E. (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 108, 1167-1174

2. Yu, P. B., Hong, C. C., Sachidanandan, C., Babitt, J. L., Deng, D. Y., Hoyng, S. A., Lin, H. Y., Bloch, K. D. and Peterson, R. T. (2008) Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 4, 33-41

质量控制

化学结构

Dorsomorphin 2HCl