ESI-09

Category	Virus Protease
CAS	263707-16-0
Description	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.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.

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Product Information

Synonyms	ESI09; ESI 09; ESI-09.
IUPAC Name	(1E)-2-(5-tert-butyl-1,2-oxazol-3-yl)-N-(3-chloroanilino)-2-oxoethanimidoyl cyanide
Molecular Weight	330.77
Molecular Formula	C16H15ClN4O2
Canonical SMILES	CC(C)(C)C1=CC(=NO1)C(=O)C(=NNC2=CC(=CC=C2)Cl)C#N
InChI	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+
InChIKey	DXEATJQGQHDURZ-DEDYPNTBSA-N
Purity	>98%
Solubility	In Vitro: DMSO : ≥ 47 mg/mL(142.09 mM) In Vivo: 1.Add each solvent one by one:10% DMSO >> 40%PEG300 >> 5%Tween-80 >> 45% saline Solubility: ≥ 2.5 mg/mL (7.56 mM); Clear solution 2.Add each solvent one by one:10% DMSO >> 90%corn oil Solubility: ≥ 2.5 mg/mL (7.56 mM); Clear solution
Appearance	Off-white to orange (Solid)
Storage	Powder: -20°C: 3 years 4°C: 2 years In solvent: -80°C: 6 months -20°C: 1 month
Animal Admin	ESI-09 is dissolved in buffered saline containing 10% (vol/vol) ethanol and 10% (vol/vol) Tween-80. Thirty-three WT C57BL/6 mice are divided into four groups [11 mice (group A), 10 mice (group B), 6 mice each (groups C and D)]. Groups A and C are treated with the Epac-specific inhibitor ESI-09 [10 mg/kg ] via i.p. injection for 5 d before infection, whereas groups B and D are treated with vehicle, followed by i.v. inoculation of R. australis for groups A and B or mock inoculation for groups C and D. ESI-09 or vehicle treatment is continued for another 7 d until mice are killed on day 8. During the course of the experiments, animals are monitored daily for signs of illness and mortality.
Complexity	520
Exact Mass	330.0883534
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. 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.
PSA	91.28000
Target	IC50: 3.2 μM (EPAC1), 1.4 μM (EPAC2)
XLogP3-AA	5.2