ESI 05 is a selective EPAC2 inhibitor. It inhibits cAMP binding to EPAC2 and cAMP mediated EPAC2 guanine nucleotide exchange factor (GEF) activity (IC50=0.4μM)[1]. It has been tested the ability of ESI 05 to compete with the binding of 8-NBD-cAMP to EPAC2. ESI-05 showed an increased potency with apparent IC50 of 0.4 ± 0.1μM, representing a 100- or 67-fold increase in affinity over cAMP[2]. ESI-05 (1, 5, 10, and 25 µM) reduces activation of the GTPase RAP1 induced by the Epac-selective cAMP analog 007-AM in HEK293 cells expressing Epac2 but has no effect in HEK293 cells expressing Epac1.
ESI-05 细胞实验
Cell Line
Concentration
Treated Time
Description
References
NAc slices
20 µM
40 minutes
To investigate the effect of Epac2 inhibitor ESI-05 on dopamine release, results showed that ESI-05 blocked the S-220-induced increase in dopamine release
Elife. 2022 Aug 22;11:e80747.
HEK293/EPAC1 cells
25 μM
5 minutes
ESI-05 had no inhibitory effect on EPAC1
Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18613-8.
Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18613-8.
Human pancreatic α-cells
25μM
90 minutes
Inhibition of EPAC2 significantly reduced adrenaline-induced [Ca2+]i increase and glucagon secretion
Diabetes. 2018 Jun;67(6):1128-1139.
Mouse pancreatic α-cells
25μM
90 minutes
Inhibition of EPAC2 significantly reduced adrenaline-induced [Ca2+]i increase and glucagon secretion
Diabetes. 2018 Jun;67(6):1128-1139.
NRK49F cells
3 μmol/L
1 hour
To investigate the inhibitory effect of ESI-05 on TGF-β1-induced α-SMA expression
J Cell Mol Med. 2019 Feb;23(2):1608-1612.
ESI-05 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Epac2 conditional knockout mice
Intraperitoneal injection
3.3 or 10 mg/kg
Single injection, tested 10 minutes later
To investigate the effect of Epac2 inhibition on cocaine self-administration, results showed that ESI-05 dose-dependently reduced cocaine intake
Elife. 2022 Aug 22;11:e80747.
Mice
High-fat diet-induced obesity model
Intracerebroventricular injection
0.2 nmol/brain/day
Once daily for 14 days
ESI-05 significantly reversed leptin resistance and reduced body weight and food intake in HFD-induced obese mice.
Cell Rep. 2016 Sep 13;16(11):3003-3015
Mice
Epac WT, Epac1–/–, Epac2–/–, and Epac1&2–/– mice
Intraperitoneal injection
5 μM
15 minutes
ESI-05 significantly decreased ENaC activity in Epac WT mice on a sodium-deficient diet but had no significant effect on mice on a regular diet.
JCI Insight. 2022 Feb 8;7(3):e145653
Adult female Sprague Dawley rats
Spinal cord contusion model
Intrathecal administration
15 µM
Continuous for 1 week
To investigate the role of EPAC2 in NPC transplantation-mediated treatment mechanisms for SCI. Results showed that NPC transplantation combined with ESI-05 treatment increased rostral cAMP levels but reduced EPAC2 mRNA levels, increased scar area, polarized microglia into an inflammatory phenotype, and enlarged the gap between NeuN+ cells.
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