5.00506

EPAC Inhibitor, ESI-09

• Synonym(s): EPAC Inhibitor, ESI-09, 3-(5- tert-butyl-isoxazol-3-yl)-2-((3-chlorophenyl)-hydrazono)-3-oxo-propionitrile, cAMP -GEF Inhibitor, Exchange Protein Directly Activated by cAMP Inhibitor
• Empirical Formula (Hill Notation): C₁₆H₁₅ClN₄O₂
• CAS Number: 263707-16-0
• Molecular Weight: 330.77
• UNSPSC Code: 12352200

Properties

• Assay: ≥98% (HPLC)
• Quality Level: 100
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: yellow
• solubility: DMSO: 100 mg/mL
• storage temp.: 2-8°C

Description

General description

A cell-permeable compound that targets cAMP-binding domain of EPAC/cAMP-GEF and inhibits cAMP-dependent EPAC GEF activity (IC₅₀ = 1.4 and 3.2 µM, respectively, against EPAC2 and EPAC1).

A cell-permeable propionitrile compound that targets the CBD (cAMP-binding domain) of EPAC/cAMP-GEF with 4-fold higher affinity than cAMP and selectively inhibits cAMP-dependent EPAC GEF activity (IC₅₀ = 1.4 and 3.2 M, respectively, against EPAC2 and EPAC1; [cAMP] = 25 M) with much reduced potency toward cAMP-dependent PKA activity (10% and 20% inhibition at 100 M, respectively, against 100 M cAMP-stimulated Type Iα and IIβ PKA activity). Shown to block both basal and 8-CPT-2′-O-Me-cAMP (Cat. No. 116833) prodrug 007-AM-, but not EGF-, stimulated Akt phosphorylations in serum-starved human AsPC-1 (≥185%, ≤85%, and <10% of basal thr308/Ser473 phosphorylation, respectively, with 0, 1, 10 M ESI-09; [007-AM] = 10 M) and EPAC-mediated insulin secretion from rat INS-1 cells (IC₅₀<5 M; [007-AM] = 10 M).

A cell-permeable, propionitrile compound that targets the CBD (cAMP-binding domain) of EPAC/cAMP-GEF with 4-fold higher affinity than cAMP (IC₅₀ = 10 vs. 39 µM, respectively, against 8-NBD-cAMP in competition EPAC2 binding assay) and selectively inhibits cAMP-dependent EPAC GEF activity (IC₅₀ = 1.4 and 3.2 µM, respectively, against EPAC2 and EPAC1; [cAMP] = 25 µM) with much reduced potency toward cAMP-dependent PKA activity (10% and 20% inhibition at 100 µM, respectively, against 100 µM cAMP-stimulated Type Iα and IIβ PKA activity). Shown to block both basal and 8-CPT-2′-O-Me-cAMP (Cat. No. 116833) prodrug 007-AM-stimulated Akt thr308/Ser473 phosphorylations in serum-starved human pancreatic cancer AsPC-1 (%thr308/%Ser473 of basal phosphorylation = 200%/185%, 85%/65%, and <10%/<10%, respectively, with 0, 1, 10 µM ESI-09; [007-AM] = 10 µM) and rat pancreatic β-cell INS-1 without affecting EGF-stimulated Akt phosphorylations, resulting in effective inhibition of EPAC-mediated insulin secretion from INS-1 cells (by 57% and 100%, respectively, at 5 and 10 µM; [007-AM] = 10 µM) and pancreatic cancer cell invasion (~60% inhibition at 5 µM using AsPC-1 and PANC-1 cells).

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Almahariq, M., et al. 2013. Mol Pharmacol.83, 122.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable