ESI-09


Catalog No. size PriceQuantity
M6558-2 2mg solid $100
M6558-10 10mg solid $396

Description

Cas:263707-16-0

Product Information:

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 Formula: C16H15ClN4O2

 

Exact Mass: 330.08835

 

Molecular Weight: 330.77

 

Elemental Analysis: C, 58.10; H, 4.57; Cl, 10.72; N, 16.94; O, 9.67

 

Synonym:

 

ESI09

ESI 09

ESI-09

 

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

 

 

Technical Data:

 

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

 

In Vitro

While cAMP competes with 8-NBD-cAMP binding with an IC50 of 39 µM, ESI-09 shows an increased potency with an apparent IC50 of 10 µM. ESI-09 inhibis cAMP-mediated EPAC2 and EPAC1 GEF activity with an IC50 of 1.4 and 3.2µM, respectively. ESI-09 could fit well into the functional cAMP-binding pocket of EPAC1, establishing favorable hydrophobic and hydrogen bonding interactions with the protein’s active-site residues. ESI-09 inhibits 007-AM-stimulated Akt phosphorylation at T308 and S473 in a dose-dependent manner. ESI-09 inhibits pancreatic cancer cells AsPC-1 and PANC-1 migration. ESI-09 inhibits EPAC1-mediated adhesion of PDA cells on collagen I[1]. Exposure to ESI-09 significantly reduces intracellular and total bacterial counts in HUVECs at 30 min postinfection with 10 multiplicities of infection (MOI) of R. australis compared with similarly infected controls.

 

In Vivo

Treatment with ESI-09 dramatically protects WT mice against R. australis infection with much milder disease manifestations and significantly improves survival.

 

 

References

 

  1. 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.

 

  1. 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.

 

  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. PubMed PMID: 24218580; PubMed Central PMCID: PMC3845138.

 

  1. 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.

 

Products are for research use only. Not for human use.

 

 

 

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