ESI-09
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406603

CAS#: 263707-16-0

Description: ESI-09 is a novel noncyclic nucleotide EPAC antagonist that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as EPAC-mediated insulin secretion in pancreatic β cells. EPAC1 plays an important role in pancreatic cancer cell migration and invasion, and thus represents a potential target for developing novel therapeutic strategies for pancreatic cancer.

Chemical Structure

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ESI-09
CAS# 263707-16-0
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406603
Name: ESI-09
CAS#: 263707-16-0
Chemical Formula: C16H15ClN4O2
Exact Mass: 330.09
Molecular Weight: 330.770
Elemental Analysis: C, 58.10; H, 4.57; Cl, 10.72; N, 16.94; O, 9.67

Price and Availability

Size Price Availability Quantity
10mg USD 125 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to ship
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Synonym: ESI09; ESI 09; ESI-09.

IUPAC/Chemical Name: (E)-2-(5-(tert-butyl)isoxazol-3-yl)-N'-(3-chlorophenyl)-2-oxoacetohydrazonoyl cyanide

InChi Key: DXEATJQGQHDURZ-DEDYPNTBSA-N

InChi Code: InChI=1S/C16H15ClN4O2/c1-16(2,3)14-8-12(21-23-14)15(22)13(9-18)20-19-11-6-4-5-10(17)7-11/h4-8,19H,1-3H3/b20-13+

SMILES Code: N#C/C(C(C1=NOC(C(C)(C)C)=C1)=O)=N\NC2=CC=CC(Cl)=C2

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:         

Biological target: ESI-09 is a specific exchange protein directly activated by cAMP (EPAC) inhibitor with IC50 of 3.2 μM and 1.4 μM for EPAC1 and EPAC2, respectively, >100-fold selectivity over PKA.
In vitro activity: To test whether our newly identified EPAC antagonist ESI-09 is capable of modulating EPAC activation in living cells, its ability to suppress Akt phosphorylation was monitored as EPAC proteins are also known to activate Akt signaling, whereas PKA inhibits it. To determine whether ESI-09 is capable of blocking EPAC-mediated Akt activation, the phosphorylation status of T308 and S473 of Akt in the pancreatic cancer cell line AsPC-1, which overexpresses EPAC1, was followed using anti-phospho-Akt antibodies. As shown in Fig. 4, ESI-09 inhibited 007-AM-stimulated Akt phosphorylation at T308 and S473 in a dose-dependent manner. Similar results were observed in the rat pancreatic β-cell line INS-1 (Supplemental Fig. 3). On the other hand, ESI-09 failed to suppress epidermal growth factor (EGF)-induced phosphorylation of Akt in AsPC1 cells (Fig. 4). Reference: Mol Pharmacol. 2013 Jan;83(1):122-8. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23066090/
In vivo activity: WT C57BL/6 mice, randomly divided into two groups, were treated with ESI-09 (10 mg⋅kg−1⋅d−1) or vehicle via i.p. injection for 5 d, followed by i.v. inoculation of R. australis. ESI-09 treatment was continued for another 7 d. As shown in Fig. 5, treatment with ESI-09 dramatically protected WT mice against R. australis infection with much milder disease manifestations (Fig. 5A) and significantly improved survival (Fig. 5B). Only 1 of 11 ESI-09–treated mice died (9% mortality), compared with those of the vehicle-only group, in which 6 of 10 WT mice died (60% mortality) at the end of experiment. Histological evaluation confirmed that pharmacological inhibition of Epac significantly attenuated the pathological responses, resulting in milder vasculitis in the testis, occasional microvesicular hepatocellular fatty change, less interstitial inflammation in the lung, and immunohistochemical evidence of significantly less rickettsial antigen in tissues compared with the control group (Fig. 5C). Reference: Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19615-20. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24218580/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 66.0 199.53
Ethanol 20.0 60.46

Preparing Stock Solutions

The following data is based on the product molecular weight 330.77 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol: 1. Almahariq M, Tsalkova T, Mei FC, Chen H, Zhou J, Sastry SK, Schwede F, Cheng X. A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Mol Pharmacol. 2013 Jan;83(1):122-8. doi: 10.1124/mol.112.080689. Epub 2012 Oct 11. PMID: 23066090; PMCID: PMC3533471. 2. Wang X, Luo C, Cheng X, Lu M. Lithium and an EPAC-specific inhibitor ESI-09 synergistically suppress pancreatic cancer cell proliferation and survival. Acta Biochim Biophys Sin (Shanghai). 2017 Jul 1;49(7):573-580. doi: 10.1093/abbs/gmx045. PMID: 28475672.
In vivo protocol: 1. Gong B, Shelite T, Mei FC, Ha T, Hu Y, Xu G, Chang Q, Wakamiya M, Ksiazek TG, Boor PJ, Bouyer DH, Popov VL, Chen J, Walker DH, Cheng X. Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19615-20. doi: 10.1073/pnas.1314400110. Epub 2013 Nov 11. PMID: 24218580; PMCID: PMC3845138.

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1: Aslam M, Tanislav C, Troidl C, Schulz R, Hamm C, Gündüz D. cAMP controls the restoration of endothelial barrier function after thrombin-induced hyperpermeability via Rac1 activation. Physiol Rep. 2014 Oct 24;2(10). pii: e12175. doi: 10.14814/phy2.12175. Print 2014 Oct 1. PubMed PMID: 25344477; PubMed Central PMCID: PMC4254100.

2: Mediero A, Perez-Aso M, Cronstein BN. Activation of EPAC1/2 is essential for osteoclast formation by modulating NFκB nuclear translocation and actin cytoskeleton rearrangements. FASEB J. 2014 Nov;28(11):4901-13. doi: 10.1096/fj.14-255703. Epub 2014 Aug 13. PubMed PMID: 25122553; PubMed Central PMCID: PMC4200330.

3: Bacallao K, Monje PV. Opposing roles of PKA and EPAC in the cAMP-dependent regulation of schwann cell proliferation and differentiation [corrected]. PLoS One. 2013 Dec 11;8(12):e82354. doi: 10.1371/journal.pone.0082354. eCollection 2013. Erratum in: PLoS One. 2014;9(1). doi:10.1371/annotation/fa651e8d-ed5a-4937-8d7e-8009b10dcbe0. PubMed PMID: 24349260; PubMed Central PMCID: PMC3859537.

4: Gong B, Shelite T, Mei FC, Ha T, Hu Y, Xu G, Chang Q, Wakamiya M, Ksiazek TG, Boor PJ, Bouyer DH, Popov VL, Chen J, Walker DH, Cheng X. Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19615-20. doi: 10.1073/pnas.1314400110. Epub 2013 Nov 11. PubMed PMID: 24218580; PubMed Central PMCID: PMC3845138.

5: Li X, Guo Q, Gao J, Yang J, Zhang W, Liang Y, Wu D, Liu Y, Weng J, Li Q, Zhang Y. The adenylyl cyclase inhibitor MDL-12,330A potentiates insulin secretion via blockade of voltage-dependent K(+) channels in pancreatic beta cells. PLoS One. 2013 Oct 29;8(10):e77934. doi: 10.1371/journal.pone.0077934. eCollection 2013. PubMed PMID: 24205033; PubMed Central PMCID: PMC3812155.

6: Rehmann H. Epac-inhibitors: facts and artefacts. Sci Rep. 2013 Oct 23;3:3032. doi: 10.1038/srep03032. PubMed PMID: 24149987; PubMed Central PMCID: PMC3805970.

7: Chen H, Ding C, Wild C, Liu H, Wang T, White MA, Cheng X, Zhou J. Efficient Synthesis of ESI-09, A Novel Non-cyclic Nucleotide EPAC Antagonist. Tetrahedron Lett. 2013 Mar 20;54(12):1546-1549. PubMed PMID: 23459418; PubMed Central PMCID: PMC3580859.

8: Almahariq M, Tsalkova T, Mei FC, Chen H, Zhou J, Sastry SK, Schwede F, Cheng X. A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Mol Pharmacol. 2013 Jan;83(1):122-8. doi: 10.1124/mol.112.080689. Epub 2012 Oct 11. PubMed PMID: 23066090; PubMed Central PMCID: PMC3533471.