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ESI-09

现货
Catalog No.
B4814
EPAC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
5mg
¥ 680.00
现货
25mg
¥ 2,080.00
现货
100mg
¥ 4,740.00
现货

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Background

ESI-09 is a specific inhibitor of EPAC with IC50 values of 1.4 and 3.2 µM for EPAC2 and EPAC1, respectively [1].

cAMP/cAMP regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) is a guanine nucleotide exchange factor for small GTPases Rap1 and Rap2 in response to intracellular cAMP [2].

ESI-09 is a specific EPAC inhibitor. ESI-09 (25 µM) reduced EPAC1 and EPAC2 GEF activity to basal levels in the presence of 25 µM cAMP. In the presence of 25 µM cAMP, ESI-09 inhibited cAMP-mediated EPAC2 and EPAC1 GEF activity with IC50 values of 1.4 and 3.2 µM respectively and exhibited 100 times selectivity than PKA. In the pancreatic cancer cell line AsPC-1, ESI-09 inhibited Akt phosphorylation at T308 and S473 stimulated by 007-AM in a dose dependent way. In pancreatic endocrine β cells, ESI-09 inhibited the increase of insulin secretion stimulated by 007-AM in a dose dependent way. In pancreatic cancer cell lines AsPC-1 and PANC-1, ESI-09 significantly reduced cell migration through the inhibition of EPAC1 [1]. In the presence of 20 µM cAMP, ESI-09 inhibited cAMP-mediated EPAC2 and EPAC1 GEF activity with IC50 values of 4.4 and 10.8 µM, respectively [2].

References:
[1].  Almahariq M, Tsalkova T, Mei FC, et al. A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Mol Pharmacol, 2013, 83(1): 122-128.
[2].  Zhu Y, Chen H, Boulton S, et al. Biochemical and pharmacological characterizations of ESI-09 based EPAC inhibitors: defining the ESI-09 ""therapeutic window"". Sci Rep, 2015, 5: 9344.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt330.77
Cas No.263707-16-0
FormulaC16H15ClN4O2
Solubility≥33.1mg/mL in DMSO
Chemical Name(1E)-2-(5-tert-butyl-1,2-oxazol-3-yl)-N-(3-chloroanilino)-2-oxoethanimidoyl cyanide
SDFDownload SDF
Canonical SMILESCC(C)(C)C1=CC(=NO1)C(=O)C(=NNC2=CC(=CC=C2)Cl)C#N
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 [1,2]:

细胞系

AsPC-1和PANC-1胰腺癌细胞,INS-1细胞

溶解方法

该化合物在DMSO中的溶解度大于16.6 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

10 μM,5分钟

应用

在AsPC-1胰腺癌细胞中,ESI-09(1 μM,10μM,5分钟)抑制EPAC介导的Akt磷酸化。在INS-1细胞中,ESI-09(5 μM,10 μM)抑制EPAC2介导的胰岛素分泌。ESI-09(5 μM,10 μM)抑制胰腺癌迁移。在AcPC-1和PANC-1细胞中,ESI-09预处理15分钟以剂量依赖性方式降低了007-AM诱导的细胞粘附。ESI-09显著降低人脐静脉内皮细胞的细胞内和细菌总数。

动物实验 [2]:

动物模型

C57BL/6 Epac1缺失小鼠

给药剂量

腹腔注射,10 mg/kg/d,5天

应用

ESI-09 (10 mg/kg/d, i.p.)治疗5天通过药理学抑制EPAC1,保护野生型C57BL/6小鼠免死于致命的SFG立克次体症。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Almahariq M, Tsalkova T, Mei F C, et al. A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion[J]. Molecular pharmacology, 2013, 83(1): 122-128.

[2]. Gong B, Shelite T, Mei F C, et al. Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses[J]. Proceedings of the National Academy of Sciences, 2013, 110(48): 19615-19620.

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