ESI-05 (also known as NSC 116966) is a novel, potent and specific antagonist of EPAC2 (exchange protein directly activated by cAMP 2), with an IC50 of 0.4 µM. ESI-05 prevents both EAPC2-mediated Rap1 activation and cAMP-mediated EPAC2 activation.

Physicochemical Properties

Molecular Formula	C16H18O2S
Molecular Weight	274.37792
Exact Mass	274.103
Elemental Analysis	C, 70.04; H, 6.61; O, 11.66; S, 11.68
CAS #	5184-64-5
PubChem CID	272513
Appearance	White to off-white solid powder
Density	1.129g/cm3
Boiling Point	426.7ºC at 760mmHg
Flash Point	250ºC
Index of Refraction	1.562
LogP	4.833
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	2
Heavy Atom Count	19
Complexity	376
Defined Atom Stereocenter Count	0
SMILES	CC1=CC=C(C=C1)S(=O)(=O)C2=C(C=C(C=C2C)C)C
InChi Key	CGPHOZWFSFNOEQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H18O2S/c1-11-5-7-15(8-6-11)19(17,18)16-13(3)9-12(2)10-14(16)4/h5-10H,1-4H3
Chemical Name	1,3,5-trimethyl-2-(4-methylphenyl)sulfonylbenzene
Synonyms	ESI-05; NSC-116966; ESI05; NSC116966; ESI 05; NSC 116966
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	EPAC2 ( IC50 = 0.43 μM )
ln Vitro	ESI-05 (0.01 μM-1 nM) inhibits cAMP-mediated EPAC2 GEF activity with an IC50 of 0.43 μM, but is completely blank in inhibiting EPAC1 GEF activity [1]. ESI-05 (1, 5, 10, and 25 μM; 5 Western Blot Analysis[1] Cell Line: HEK293 cells Concentration: 1, 5, 10, and 25 μM Incubation Time: 5 min Results: Results in dose-dependent manner. EPAC Selection A cAMP analog (007-AM) induces a reduction in Rap1 activation.
ln Vivo	ESI-05 (2, 4 and 8 mg/kg) reduces neuronal cells in vivo by inhibiting p38/BIM [2]. Animal model: Intracranial hemorrhage (ICH) model [2] Dosage: 2, 4, 8 mg/kg Administration: Results: Decreased apoptosis rate of cortical nerve cells, phosphorylated p38, Bcl-2like protein 11 (BIM) and caspase- 3 Protein expression decreased accordingly.
Cell Assay	Cell Line: HEK293 cells Concentration: 1, 5, 10, and 25 μM Incubation Time: 5 min Result: Led to a dose-dependent reduction of the EPAC-selective cAMP analog (007-AM) induced Rap1 activation.
Animal Protocol	Intracranial hemorrhage (ICH) model 2, 4, and 8 mg/kg
References	[1]. Isoform-specific antagonists of exchange proteins directly activated by cAMP. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18613-8. [2]. Inhibition of EPAC2 Attenuates Intracerebral Hemorrhage-Induced Secondary Brain Injury via the p38/BIM/Caspase-3 Pathway. J Mol Neurosci. 2019 Mar;67(3):353-363.

Solubility Data

Solubility (In Vitro)

DMSO: 50~55 mg/mL (182.2~200.5 mM) Ethanol: ~55 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.6446 mL	18.2229 mL	36.4458 mL
	5 mM	0.7289 mL	3.6446 mL	7.2892 mL
	10 mM	0.3645 mL	1.8223 mL	3.6446 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.