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EMD638683

现货
Catalog No.
A3389
SGK1 抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,850.00
现货
5mg
¥ 2,610.00
现货
10mg
¥ 3,360.00
现货
50mg
¥ 9,060.00
现货
200mg
¥ 20,570.00
现货

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Background

EMD638683 is a highly selective inhibitor of the serum and glucocorticoid inducible kinase (SGK) with IC50 value of 3 μM [1].
SGK is a group of serine/threonine kinases that consists of SGK1, SGK2 and SGK3. Among these, SGK1 takes participate in the signaling pathway that regulates the sodium channel, cell proliferation, cell survival and many other cellular processes. The transcription of SGK1 can be up-regulated by the activation of serum, mineralocorticoids and glucocorticoids. SGK1 enhanced the renal tubular reabsorption of sodium after the high salt activation. Besides that, SGK is highly expressed in some sorts of tumors while down-regulated in some other tumors such as APC. The selective SGK1 inhibitor EMD638683 showed inhibition effects on all the three forms of SGK but not for other kinases. It can affect the phosphorylation of NDRG1in vitro and meanwhile exert anti-tumor or anti-hypertensive efficacy in vivo [1, 2].
In the biochemical kinase assays, EMD638683 at concentration of 1 μM inhibited 85%, 71% and 75% activities of SGK1, SGK2 and SGK3, respectively. It also had inhibitory effects on MSK1 (mitogen-and stress-activated protein kinase 1) and PRK2 (protein kinase C-related kinase 2) with IC50 values of ≤ 1 μM. For other 64 kinases, such as MAPK, PRAK and Syk, EMD638683 showed no significant inhibition. In HeLa cells, EMD638683 suppressed the phosphorylation of NDRG1, which is a target of SGK1, with IC50 value of 3.35 μM. Besides that, EMD638683 treated CaCo-2 cells displayed increased depolarized mitochondria and enhanced caspase activity after the exposure to radiation [1, 2].
In mice treated with the carcinogenic drugs, the administration of EMD638683 at dose of 600 mg/kg/day significantly lowered the colon weight and reduced the developing tumors. In another mice experiment, administration of EMD638683 increased the urinary output and normalized the systolic blood pressure in mice treated with 10% fructose drinking water. It indicated that EMD638683 might be an attracted drug for the hypertension treatment in diabetic patients [1, 2].
References:
[1] Towhid S T, Liu G L, Ackermann T F, et al. Inhibition of colonic tumor growth by the selective SGK inhibitor EMD638683. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology, 2012, 32(4): 838-848.
[2] Ackermann T F, Boini K M, Beier N, et al. EMD638683, a novel SGK inhibitor with antihypertensive potency. Cellular Physiology and Biochemistry, 2011, 28(1): 137-146.

文献引用

1. Greenawalt EJ, Edmonds MD, et al. "Targeting of SGK1 by miR-576-3p Inhibits Lung Adenocarcinoma Migration and Invasion." Mol Cancer Res. 2018 Sep 26. PMID:30257988
2. Schmid E, Stagno MJ, et al. "Serum and Glucocorticoid Inducible Kinase 1-Sensitive Survival,Proliferation and Migration of Rhabdomyosarcoma Cells." Cell Physiol Biochem. 2017 Oct 9;43(3):1301-1308. PMID:28992614
3. Mason JA, Davison-Versagli CA, et al. "Oncogenic Ras differentially regulates metabolism and anoikis in extracellular matrix-detached cells." Cell Death Differ. 2016 Feb 26. PMID:26915296
4. Dr.Alvaro Diaz. "Condicionamiento de células dendríticas por la capa laminar de Echinococcus granulosus: búsqueda de agonistas y mecanismos a nivel de se?alizacón." colibri.udelar.edu.uy.2016.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt364.34
Cas No.1181770-72-8
FormulaC18H18F2N2O4
SynonymsEMD 638683;EMD-638683
Solubility≥18.2 mg/mL in DMSO, ≥45.8 mg/mL in EtOH with gentle warming, <2.66 mg/mL in H2O
Chemical NameN'-[2-(3,5-difluorophenyl)-2-hydroxyacetyl]-2-ethyl-4-hydroxy-3-methylbenzohydrazide
SDFDownload SDF
Canonical SMILESCCC1=C(C=CC(=C1C)O)C(=O)NNC(=O)C(C2=CC(=CC(=C2)F)F)O
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

HeLa细胞

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

10 μM;24 h

应用

EMD638683是SGK1的抑制剂,可抑制其特异性靶点NDRG1蛋白(N-Myc下游调节基因1)的磷酸化,IC50值为3.35 μM。

动物实验[1]:

动物模型

SGK1缺陷小鼠(sgk1-/-)

剂量

600 mg/kg,4天

准备方法

ST2825溶于0.5%羧甲基纤维素[1]

应用

在小鼠中,用10%果糖代替饮用水,连续3周,用于诱导高胰岛素血症。EMD638683治疗4天后导致收缩压正常(从111 ± 4到87 ± 3 mmHg)。EMD638683对流体和食物摄入量以及尿Na+和K+排泄均没有显著影响,但显著增加尿量和减少体重。

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] Ackermann T F, Boini K M, Beier N, et al. EMD638683, a novel SGK inhibitor with antihypertensive potency. Cellular Physiology and Biochemistry, 2011, 28(1): 137-146.

生物活性

描述 EMD638683是一个有效的SGK1抑制剂,IC50值为3 μM。
靶点 SGK1          
IC50 3 μM          

质量控制

化学结构

EMD638683

相关生物数据

EMD638683

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EMD638683

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EMD638683

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EMD638683

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EMD638683