| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
E1231 targets Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase involved in the regulation of cholesterol and lipid metabolism. It also targets liver X receptor-alpha (LXRα), which it deacetylates. By activating SIRT1 and deacetylating LXRα, E1231 increases ABCA1 expression. This promotes cholesterol efflux and reduces lipid accumulation in macrophages.
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| ln Vitro |
In RAW 264.7 cells, E1231 (0.1–10 μM; 18 hours) inhibits accumulation and encourages reflux [1]. In HepG2 cells, E1231 (10 μM; 6 hours) dramatically boosts Doxo-induced p53 dephospholipidation [1]. 1.].
In vitro, E1231 activates SIRT1 with an EC50 of 0.83 μM. It binds to recombinant human SIRT1 protein with a KD of 9.61 μM. E1231 promotes cholesterol efflux and inhibits lipid accumulation in RAW 264.7 macrophages via SIRT1 and ABCA1. It increases ABCA1 expression. These activities confirm its role in cholesterol and lipid metabolism modulation. |
| ln Vivo |
E1231 (40 mg/kg; once daily for 7 days) reduces the amount of food that golden hamsters on a high-fat diet consume on trays [1]. E1231 (once daily for 12 weeks at 25, 50, and 100 mg/kg in 0.5% CMC-Na; Manhattan) decreases the formation of atherosclerotic tumors in ApoE-/- mice without causing hepatotoxicity or nephrotoxicity.
In vivo, E1231 regulates cholesterol and lipid metabolism in hyperlipidemic golden hamsters. It decreases total cholesterol and triglyceride levels in both serum and the liver in golden hamster hyperlipidemia models. E1231 also reduces atherosclerotic plaque formation in ApoE⁻/⁻ mouse models. These findings support its potential for the treatment of atherosclerosis. |
| Enzyme Assay |
In vitro enzyme assays for E1231 measure SIRT1 activation using fluorometric or luminescent assays. Recombinant human SIRT1 enzyme is incubated with a peptide substrate and NAD⁺. Various concentrations of E1231 are added. Deacetylase activity is measured by detecting the deacetylated product using specific antibodies or fluorescent readouts. EC50 values are calculated from dose-response curves. Binding affinity (KD) is measured using surface plasmon resonance (SPR).
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| Cell Assay |
Cellular assays for E1231 use RAW 264.7 macrophages or other cell lines. Cells are treated with various concentrations of E1231. ABCA1 expression is measured by qRT-PCR or Western blotting. Cholesterol efflux is assessed by measuring the efflux of labeled cholesterol from cells. Lipid accumulation is evaluated by Oil Red O staining. These assays confirm the compound's activity.
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| Animal Protocol |
Animal/Disease Models: HFD diet golden hamster (80-90 g) [1]
Doses: 40 mg/kg Route of Administration: Oral; one time/day for 7 days Experimental Results: SIRT1 protein expression increased, but not SIRT3, SIRT6 or SIRT7. and lowered liver and serum cholesterol in hamsters. Animal/Disease Models: Atherosclerotic dietary ApoE-/- mice [1] Doses: 25, 50 and 100 mg/kg Route of Administration: Oral; one time/day for 12 weeks Experimental Results: Modulation of plaque composition, immunofluorescence staining . And diminished the CD68-positive area in the aortic sinus while increasing ABCA1 expression. In vivo animal studies for E1231 utilize hyperlipidemic golden hamsters and ApoE⁻/⁻ mouse models. The compound is administered orally at various doses. Serum and liver total cholesterol and triglyceride levels are measured. Atherosclerotic plaque formation is assessed in ApoE⁻/⁻ mice. Efficacy is compared to vehicle controls. |
| ADME/Pharmacokinetics |
E1231 has molecular weight of 363.41 g/mol and molecular formula C21H21N3O3. It is a solid with purity ≥99.0%. It is soluble in DMSO at 100 mg/mL. It is typically stored as powder at -20°C for up to 3 years or at 4°C for up to 2 years. It is orally active. Pharmacokinetic properties would be determined in preclinical studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity of E1231 has not been extensively documented. As a SIRT1 activator, potential adverse effects would be evaluated in standard toxicology studies. The compound has been studied in animal models of hyperlipidemia and atherosclerosis. No significant toxicity has been reported at efficacious doses. Standard safety pharmacology studies would assess cardiovascular, respiratory, and CNS effects.
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| References | |
| Additional Infomation |
E1231 is an orally active SIRT1 activator with an EC50 of 0.83 μM. It deacetylates LXRα and increases ABCA1 expression. It promotes cholesterol efflux and reduces lipid accumulation. It has potential for the treatment of atherosclerosis. It is available for research purposes only.
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| Molecular Formula |
C21H21N3O3
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|---|---|
| Molecular Weight |
363.42
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| Exact Mass |
363.158
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| CAS # |
1031195-19-3
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| PubChem CID |
24980435
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| Appearance |
Off-white to light brown solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
605.8±55.0 °C at 760 mmHg
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| Flash Point |
320.2±31.5 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.626
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| LogP |
1.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
27
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| Complexity |
561
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZQJTYRXKAZFWPK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H21N3O3/c1-14-7-8-20(27-14)19-13-17(16-5-3-4-6-18(16)22-19)21(26)24-11-9-23(10-12-24)15(2)25/h3-8,13H,9-12H2,1-2H3
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| Chemical Name |
1-[4-[2-(5-methylfuran-2-yl)quinoline-4-carbonyl]piperazin-1-yl]ethanone
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| Synonyms |
E1231; E 1231; E-1231
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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 |
| 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 : ~100 mg/mL (~275.17 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.88 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 (6.88 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7516 mL | 13.7582 mL | 27.5164 mL | |
| 5 mM | 0.5503 mL | 2.7516 mL | 5.5033 mL | |
| 10 mM | 0.2752 mL | 1.3758 mL | 2.7516 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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