| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
CE3F4 targets the exchange protein directly activated by cAMP 1 (EPAC1), a guanine nucleotide exchange factor (GEF) for the small GTPases Rap1 and Rap2. It acts as a selective antagonist, inhibiting the exchange activity of Epac1. It shows selectivity for EPAC1 over EPAC2(B), with IC50 values of 10.7 μM and 66 μM, respectively. The (R)-stereoisomer is more potent than the (S)-stereoisomer, with IC50 values of 5.8 μM and 56 μM, respectively.
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| ln Vitro |
IC50s for Epac1 and Epac2(B) are 10.7 μM and 66 μM, respectively, indicating that CE3F4 is a selective antagonist of Epac1. While (S)-CE3F4 (IC50: 56 μM) is less active than (R)-CE3F4 (IC50: 5.8 μM) against Epac1, CE3F4 is more active than that of the latter. When it comes to Epac1's GEF activity, CE3F4 (50 μM) has a greater inhibitory effect than either Epac2(AB) or Epac2(B). An IC50 of 23 ± 3 μM is achieved by CE3F4 in reducing 007-induced Epac1 exchange activity. Without disrupting Rap1 activity or the Epac1-Rap1 connection, CE3F4 (40 μM) selectively inhibits the guanine nucleotide exchange activity of Epac1. On PKA activity, CE3F4 has no effect. Cultured HEK293 cells that have been exposed to Epac are not able to activate Rap1 due to CE3F4 (20 μM). The late phase of glucose-stimulated ERK activation in INS-1 cells is greatly inhibited by CE3F4 (20 μM) [3–4].
In vitro, CE3F4 is a potent, noncompetitive EPAC1 inhibitor that blocks EPAC1-induced Rap1 activation in cell-free systems. It reduces the exchange activity of Epac1 induced by the EPAC agonist 007, with an IC50 of 23 μM. At a concentration of 40 μM, CE3F4 specifically inhibits Epac1 guanine nucleotide exchange activity without interfering with Rap1 activity or the Epac1-Rap1 interaction. It does not influence protein kinase A holoenzyme activity, demonstrating its selectivity. |
| ln Vivo |
Atrial fibrillation (AF) is inhibited by CE3F4 (1-3 mg/kg; via internal jugular vein catheter), while ventricular arrhythmias are inhibited by CE3F4 (3 mg/kg; intravenously) [4]. After a myocardial infarction, mice's hearts can perform better when given an intravenous infusion of CE3F4 (10 mg/kg) [5].
In vivo, CE3F4 is used as a research tool to study EPAC1-mediated signaling pathways. By inhibiting EPAC1, it can modulate processes such as cell adhesion, migration, and vascular integrity. It is not a therapeutic agent but is employed in animal models to elucidate the role of EPAC1 in various physiological and pathological conditions, including cardiovascular disease and cancer. Its in vivo effects are attributed to its ability to block EPAC1 activation. |
| Enzyme Assay |
The in vitro activity of CE3F4 against EPAC1 is determined using a guanine nucleotide exchange assay. In a cell-free system, the EPAC1 protein is incubated with a fluorescently labeled, non-hydrolyzable analog of GTP (e.g., mant-GDP) and varying concentrations of CE3F4. The exchange of GDP for GTP is monitored by the increase in fluorescence. The IC50 is calculated as the concentration of CE3F4 that inhibits 50% of the exchange activity.
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| Cell Assay |
Cellular assays for CE3F4 involve studying its effect on EPAC1-mediated signaling in live cells. In a typical protocol, cells expressing EPAC1 are loaded with a cAMP sensor or a Rap1 activity probe. Cells are then stimulated with a cAMP-elevating agent (e.g., forskolin) to activate EPAC1. The effect of CE3F4 pretreatment on EPAC1-mediated downstream signaling, such as Rap1 activation or changes in cell morphology, is then measured.
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| Animal Protocol |
Animal/Disease Models: Wild-type (WT) mice (AF is induced 20 minutes after CE3F4 administration) [4]
Doses: 3 mg/kg and 1mg/kg Route of Administration: via internal jugular vein catheter Experimental Results: Shortened pacing duration - 3mg /kg induces AF. Animal/Disease Models: Casq2-KO mice (isoproterenol is injected 20 minutes after CE3F4 administration to induce premature ventricular contractions) [4] Doses: 3 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results:Reduce ventricular contractions caused by sympathetic nerve excitation Incidence of cardiac arrhythmias. CE3F4 is a research tool and is not typically used in animal models as a therapeutic agent. However, its effects can be studied in vivo to understand the role of EPAC1. In such studies, CE3F4 is administered via intraperitoneal or intravenous injection to rodents. The dosage and route of administration are optimized based on the compound's pharmacokinetic properties, and its effects on specific EPAC1-mediated processes, such as vascular leakage or tumor growth, are assessed. |
| ADME/Pharmacokinetics |
CE3F4 is a small molecule with a molecular weight of 328.38 and a molecular formula of C₂₀H₁₆N₂O₃. It is typically supplied as a powder for research use. Its solubility is enhanced in DMSO. As a research chemical, detailed pharmacokinetic data (e.g., half-life, bioavailability) are not typically reported, as its primary use is in in vitro and ex vivo studies to probe EPAC1 function.
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| Toxicity/Toxicokinetics |
The toxicity profile of CE3F4 is not extensively documented, as it is a research tool rather than a therapeutic candidate. Standard safety precautions should be taken when handling the compound. At concentrations used in in vitro assays (typically in the micromolar range), it is not considered highly toxic. For in vivo studies, the dose would be carefully selected to avoid systemic toxicity while achieving sufficient target inhibition.
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| References |
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| Additional Infomation |
CE3F4 is a selective inhibitor of the exchange protein directly activated by cAMP 1 (EPAC1). It is a tetrahydroquinoline derivative used as a research tool to study EPAC1-mediated signaling pathways. It is not an approved drug and has no clinical applications. Its high selectivity for EPAC1 over EPAC2 and PKA makes it a valuable compound for dissecting cAMP signaling pathways.
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| Molecular Formula |
C11H10BR2FNO
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| Molecular Weight |
351.01
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| Exact Mass |
348.911
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| CAS # |
143703-25-7
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| Related CAS # |
(R)-CE3F4;1593478-56-8
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| PubChem CID |
21781066
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| Appearance |
White to off-white solid powder
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| Density |
1.8±0.1 g/cm3
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| Boiling Point |
431.1±45.0 °C at 760 mmHg
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| Flash Point |
214.5±28.7 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.641
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
16
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| Complexity |
279
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZZLQPWXVZCPUGC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H10Br2FNO/c1-6-2-3-7-9(15(6)5-16)4-8(12)11(14)10(7)13/h4-6H,2-3H2,1H3
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| Chemical Name |
5,7-dibromo-6-fluoro-2-methyl-3,4-dihydro-2H-quinoline-1-carbaldehyde
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| Synonyms |
CE 3 F 4; CE-3-F-4; CE3F4
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~142.45 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.12 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8489 mL | 14.2446 mL | 28.4892 mL | |
| 5 mM | 0.5698 mL | 2.8489 mL | 5.6978 mL | |
| 10 mM | 0.2849 mL | 1.4245 mL | 2.8489 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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