ESI-09
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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 330.77 |
| Cas No. | 263707-16-0 |
| Formula | C16H15ClN4O2 |
| Solubility | ≥33.1 mg/mL in DMSO; insoluble in H2O; ≥2.22 mg/mL in EtOH with ultrasonic |
| Chemical Name | (1E)-2-(5-tert-butyl-1,2-oxazol-3-yl)-N-(3-chloroanilino)-2-oxoethanimidoyl cyanide |
| SDF | Download SDF |
| Canonical SMILES | CC(C)(C)C1=CC(=NO1)C(=O)C(=NNC2=CC(=CC=C2)Cl)C#N |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1,2]: | |
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Cell lines |
AsPC-1 and PANC-1 pancreatic cancer cells, INS-1 cells |
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Preparation method |
The solubility of this compound in DMSO is > 16.6 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
10 μM, 5 minutes |
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Applications |
ESI-09 (1 μM, 10 μM, 5 minutes) inhibited EPAC-mediated Akt phosphorylation in AsPC-1 pancreatic cancer cells. ESI-09 (5 μM, 10 μM) inhibited EPAC2-mediated insulin secretion in INS-1 cells. ESI-09 (5 μM, 10 μM) inhibited pancreatic cancer migration. In both AcPC-1 and PANC-1 cells, pretreatment with ESI-09 (15 minutes) decreased 007-AM-induced cell adhesion dose-dependently. ESI-09 significantly reduced intracellular and total bacterial counts in human umbilical vein endothelial cells. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 Epac1 null mice |
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Dosage form |
Intraperitoneal injection, 10 mg/kg/d, 5 d |
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Application |
Treatment with ESI-09 (10 mg/kg/d, i.p.) for 5 days protected WT C57BL/6 mice from fatal SFG rickettsiosis via pharmacological inhibition of EPAC1. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
Quality Control & MSDS
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