AM-001
Based on 1 Customer Validation
AM-001 is a selective Epac1 inhibitor with an IC50 value of 47.8-53.7 μM. AM-001 blocks cAMP (Cyclic AMP) (HY-B1511)-induced conformational changes of Epac1, inhibits Epac1-dependent activation of Rap1, and does not compete with cAMP for binding to Epac1. AM-001 disrupts the formation of the Epac1-GRK5 complex, blocks nuclear import of GRK5, and inhibits GRK5-mediated nuclear export of HDAC5 and activation of MEF2. AM-001 can be used in research related to heart disease, myocardial ischemia/reperfusion injury, SARS-CoV-2 infection, influenza A virus infection, atrial fibrillation and idiopathic pulmonary fibrosis.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 99.95%
- No. CAS: 340817-81-4
- Fòrmula: C24H16FN3OS2
- Peso molecular:445.53
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
Descripciòn
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EPAC1 47.8-53.7 μM (IC50) |
In Vitro
AM-001 (1-1000 μM) acts as a non-competitive inhibitor of Epac1 in the CAMYEL BRET sensor assay, with an IC50 of 53.7 μM, reducing maximal cAMP (Cyclic AMP) (HY-B1511)-induced conformational changes without affecting cAMP binding affinity[1].
AM-001 (20-100 μM) selectively inhibits Epac1 (IC50 = 48.5 μM) but not Epac2 GEF activity in cell-free assays, acting as a non-competitive inhibitor relative to Epac agonists[1].
AM-001 (20 μM) does not inhibit Type I or Type II PKA activity in cell-free assays, confirming its specificity for Epac1 among cAMP-dependent effectors[1].
AM-001 (20 μM; 30 min) selectively inhibits Epac1-dependent Rap1 activation in HEK293 cells, with no effect on Epac2A or Epac2B-mediated Rap1 activation[1].
AM-001 (20 µM; 7 min before 100 µM cAMP injection) inhibits cAMP-induced EPAC1 activation in Vero E6 cell lysates[2].
AM-001 (20 μM; at least 1 h pre-incubation, 15 min superfusion) prevents the exchange protein directly activated by cyclic AMP-induced downregulation of repolarizing potassium currents (IKsus and IKpeak) in enzymatically isolated human atrial cardiomyocytes from sinus rhythm patients[3].
AM-001 (20 μM; 15 min superfusion) corrects the EPAC-dependent downregulation of repolarizing potassium currents (IKsus and IKpeak) in enzymatically isolated human atrial cardiomyocytes from atrial fibrillation patients[3].
AM-001 inhibits cAMP-induced Epac1 activation in IPF fibroblasts[4].
AM-001 (20 μM; 24 h) suppresses the expression of profibrotic genes in TGF-β1-activated normal human lung fibroblasts[4].
AM-001 (48 h) alters the transcriptomic profile of TGF-β1-stimulated normal human lung fibroblasts, downregulating profibrotic and neddylation pathway genes and highlighting FoxO3a as a key regulated transcription factor[4].
AM-001 (20 μM) suppresses activation of the STAT3, SMAD2/3, and AKT signalling pathways in idiopathic pulmonary fibrosis fibroblasts[4].
AM-001 (20 μM; 48 h) downregulates neddylation pathway gene expression and restores FoxO3a expression by reducing its phosphorylation and degradation in idiopathic pulmonary fibrosis fibroblasts[4].
AM-001 (20 μM) blocks the interaction between NEDD8 and FoxO3a in idiopathic pulmonary fibrosis fibroblasts, preventing FoxO3a neddylation and degradation[4].
AM-001 (20 μM; treated every 2 days for 10 days total) reduces fibrosis, downregulates profibrotic protein markers, and restores FoxO3a expression in ex vivo human idiopathic pulmonary fibrosis precision-cut lung slices[4].
AM-001 (20 μM; 30 min) protects primary adult wild-type mouse cardiomyocytes against hypoxia-reoxygenation-induced cell death via specific inhibition of Epac1, with no effect on Epac1-/- cardiomyocytes[1].
AM-001 (20 μM; 30 min) blocks Epac1-dependent cardiomyocyte hypertrophy in primary cardiomyocytes[1].
AM-001 (20 μM; 1 h) inhibits Epac1-dependent MEF2 transcriptional activation in primary neonatal rat ventricular cardiomyocytes treated with isoprenaline[1].
AM-001 (20 μM; 30 min) blocks isoprenaline-induced GRK5 nuclear translocation and HDAC5 nuclear export in primary neonatal rat ventricular cardiomyocytes, inhibiting prohypertrophic Epac1-GRK5 signalling[1].
AM-001 reduces the proliferation of primary neonatal rat cardiac fibroblasts[1].
AM-001 (20 μM) represses high serum- and TGF-β1-induced proliferation in normal human lung fibroblasts[4].
AM-001 (20 μM; 72 h) inhibits serum-induced proliferation in both normal human lung fibroblasts and idiopathic pulmonary fibrosis fibroblasts[4].
AM-001 (20 μM; 48 h) normalises TGF-β1 expression and reduces α-SMA and IL-6 expression in idiopathic pulmonary fibrosis fibroblasts, with no effect on basal TGF-β1 in normal human lung fibroblasts[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Primary adult wild-type and Epac1-/- mouse cardiomyocytes
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Concentration:20 μM; 20 μM 8-CPT-AM
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Incubation Time:30 min pre-incubation
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Result:Reduced HX+R-induced LDH release in wild-type cardiomyocytes, mimicking the protective effect of Epac1 deletion.
Had no effect on cell survival in Epac1-/- cardiomyocytes under NX or HX+R conditions.
Inhibited 8-CPT-AM-induced cardiomyocyte death in wild-type cells subjected to HX+R.
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Cell Line:Primary cardiomyocytes
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Concentration:20 μM
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Incubation Time:30 min pre-incubation
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Result:Inhibited 8-CPT-AM-induced cardiomyocyte hypertrophy.
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Cell Line:Primary neonatal rat ventricular cardiomyocytes (NRVMs)
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Concentration:20 μM
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Incubation Time:30 min pre-incubation; 10 min ISO treatment
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Result:Prevented ISO-induced GRK5 nuclear import and HDAC5 nuclear export.
Increased nuclear HDAC5 levels and reduced cytosolic HDAC5 levels relative to vehicle-treated cells.
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Cell Line:normal human lung (NHL) fibroblasts (FBs)
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Concentration:20 μM
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Incubation Time:24 h (pre-incubation); 24 h (TGF-β1 incubation after pretreatment)
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Result:Reduced mRNA expression levels of profibrotic markers TGF-β1, collagen type 1 α1 (COL1A1), collagen type 3 α1 (COL3A1), and connective tissue growth factor (CTGF) in TGF-β1-activated NHL-FBs.
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Cell Line:normal human lung (NHL) fibroblasts (FBs), idiopathic pulmonary fibrosis (IPF) fibroblasts (FBs)
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Concentration:20 μM
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Incubation Time:72 h
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Result:Exerted a strong antiproliferative effect on serum-induced IPF-FB proliferation.
Reduced proliferation in NHL-FBs.
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Cell Line:normal human lung (NHL) fibroblasts (FBs), idiopathic pulmonary fibrosis (IPF) fibroblasts (FBs)
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Concentration:20 μM
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Incubation Time:48 h
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Result:Abolished the elevated TGF-β1 mRNA levels in IPF-FBs without affecting basal TGF-β1 levels in NHL-FBs.
Significantly reduced mRNA expression levels of α-smooth muscle actin (α-SMA) and interleukin-6 (IL-6) in IPF-FBs.
In Vivo
AM-001 (10 mg/kg/d; i.p.; daily; day 3 to day 14) attenuates pathological cardiac remodelling, reduces fibrosis and inflammation, improves cardiac contractile function, and blocks prohypertrophic Epac1-GRK5 signalling in a mouse model of chronic β-adrenergic receptor activation[1].
AM-001 (10 mg/kg; i.p.; every other day; 14 days) attenuates bleomycin-induced pulmonary fibrosis in C57BL/6 mice by reducing fibrotic lesions, collagen deposition, profibrotic signalling, and pathological immune cell infiltration, while restoring FoxO3a expression and inhibiting neddylation pathway activity[4].
AM-001 (10 mg/kg; i.p.; every other day; 14 days) is well-tolerated and has no detectable adverse effects on healthy C57BL/6 mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 or C57BL/6-SV129 background (including Epac1 knock-out and control littermates; anaesthetized, subjected to myocardial ischaemia followed by reperfusion)[1]
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Dosage:8 mg/kg
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Administration:i.v.; single bolus
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Result:Reduced the ratio of infarct size to area-at-risk to 36%.
Produced a similar reduction in infarct size as Epac1 genetic ablation.
Had no additional effect on infarct size in Epac1-deficient mice.
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Animal Model:C57BL/6 (implanted with osmotic mini-pumps delivering isoprenaline to induce chronic β-adrenergic receptor activation)[1]
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Dosage:10 mg/kg/d
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Administration:i.p.; daily; day 3 to day 14
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Result:Reduced the left ventricular weight-to-tibia length ratio increased by chronic isoprenaline treatment.
Decreased cardiac fibrosis and inflammatory cell infiltration.
Improved cardiac contractile function via higher fractional shortening and reduced left ventricular end-systolic internal diameter.
Prevented isoprenaline-induced up-regulation of GRK5, formation of Epac1-GRK5 complexes, nuclear import of GRK5, nuclear export of HDAC5, and activation of prohypertrophic MEF2 transcriptional activity.
Caused no histopathological alterations in liver or kidney, or changes in serum AST/ALT levels.
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Animal Model:C57BL/6 (wild-type, bleomycin-induced pulmonary fibrosis)[4]
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Dosage:10 mg/kg
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Administration:i.p.; every other day; 14 days
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Result:Reduced fibrotic lesions and lung hydroxyproline content.
Decreased mRNA expression of TGF-β1, COL1A1, COL3A1, and CTGF.
Reduced mRNA expression of NAE1, UBE2M, and NEDD8.
Lowered NEDD8 protein expression and restored FoxO3a protein expression.
Reduced Epac1 expression and decreased levels of phosphorylated FoxO3a and phosphorylated SMAD2/3.
Reduced neutrophil and macrophage infiltration into the lungs.
Decreased the percentage of recruited macrophages and proliferating M2 macrophages.
Reduced the percentage of tissue-resident CD4+ T-cells.
Suppressed CD4+ T-cell activation and proliferation.
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Animal Model:C57BL/6 (wild-type, healthy)[4]
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Dosage:10 mg/kg
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Administration:i.p.; every other day; 14 days
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Result:Did not cause significant weight loss.
Did not affect lung fibrosis or collagen content.
Did not alter mRNA expression of Epac1, Epac2, profibrotic markers, neddylation pathway markers, or FoxO3a in lung tissue.
Did not impact right ventricular Epac1/Epac2 expression, right ventricular hypertrophy, remodelling, or related mRNA markers.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 340817-81-4
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Appearance Solid
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Peso molecular 445.53
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Fòrmula C24H16FN3OS2
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Color Light yellow to yellow
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SMILES
NC1=C(C(NC2=CC=C(F)C=C2)=O)SC3=C1C(C4=CC=CC=C4)=CC(C5=CC=CS5)=N3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 1 mg/mL (2.24 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureza y Documentación
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Ficha de datos (302 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Laudette M, et al. Identification of a pharmacological inhibitor of Epac1 that protects the heart against acute and chronic models of cardiac stress. Cardiovascular research. 2019 Oct 01;115(12):1766-1777. [Content Brief]
[3]. Boileve A, et al. Deciphering pro-arrhythmogenic mechanisms of EPAC in human atrial cardiomyocytes. The Journal of physiology. 2025 Oct 09. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2445 mL | 11.2226 mL | 22.4452 mL | 56.1129 mL |
AM-001 Related Classifications
HY-126133 Related Classifications
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