| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
ACAT
Cholesterol acyltransferase (ACAT/SOAT) |
|---|---|
| ln Vitro |
When HepG2 cells are subjected to hypoxia, VULM1457 (0.03 and 0.1 µM) dramatically down-regulates particular AM receptors on the cells, resulting in decreased AM secretion[1]. Cell growth brought on by AM is negatively regulated by VULM1457[1]. When HepG2 cells are preincubated with VULM1457 (0.1 µM), the overall number of particular [125I]AM bindings found on the cells at unaffected affinity is greatly decreased. HepG2 cells' properties of AM binding are considerably altered when high doses of VULM1457 (1.0 and 10.0 µM) are preincubated with them[1]. HepG2 cells that are hypoxic (BmaxHypox = 127±10, KD = 0.06±0.11 nM) exhibit a considerable reduction in specific [125I]AM binding upon preincubation with VULM1457 (0.1 µM). Higher doses of VULM1457 (1.0 and 10.0 µM) result in a reduction in the total number of cells, while preincubation with VULM1457 (0.1 µM) considerably increases the number of cells (24.2±6%). The decreases in [125I]AM specific binding to HepG2 cells are significantly reduced at high concentrations of VULM1457 (1.0 and 10.0 µM)[1].
VULM 1457 is an Acyl-CoA:cholesterol acyltransferase (ACAT) or SOAT inhibitor. It decreases cholesterol levels in the liver and plasma. It significantly reduces the production and secretion of adrenomedullin (AM) and downregulates AM receptors on human hepatoblasts. It has potential for studying diabetes and hypercholesterolemia. |
| ln Vivo |
In animal models of experimental atherosclerosis, VULM 1457 dramatically lowers atherogenic activity[1]. In vivo ischaemia/reperfusion damage to the hearts of diabetic-hypercholesterolemic rats is prevented by VULM 1457[2]. Plasma total cholesterol levels are dramatically reduced by VULM 1457 (50 mg/kg/day; added as an admixture to the fat-cholesterol diet for 5 days) (1.7±0.1 mM vs. 2.9±0.5 mM in diabetic–hypercholesterolaemic animals). In the liver of DM-HCH rats, VULM 1457 similarly has a hypolipidaemic impact (3.9±0.2 mg/g vs. 7.4±1.0 mg/g)[2].
VULM 1457 (50 mg/kg/day, administered as an admixture to a fat-cholesterol diet for 5 days) significantly decreases plasma total cholesterol in diabetic-hypercholesterolemic rats. It improves overall myocardial ischemia-reperfusion injury outcomes by suppressing arrhythmogenesis and reducing myocardial necrosis. In hypercholesterolemic hamsters fed a high-cholesterol lipid diet, VULM 1457 improves real-time red blood cell flow in paw microcirculation. It significantly reduces atherogenic activity in animal experimental atherosclerosis models. |
| Enzyme Assay |
Recombinant human ACAT is expressed in insect cells, and microsomal fractions are prepared. The enzyme activity assay uses [14C]-oleoyl-CoA as the acyl donor and cholesterol as the acceptor. Reactions are incubated at 37degC for 10-30 minutes in buffer containing potassium phosphate (pH 7.4), BSA, and DTT. Product (cholesteryl oleate) is separated by TLC and quantified by radiometric detection or scintillation counting. IC50 values are determined from dose-response curves.
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| Cell Assay |
Human hepatoblastoma cells (e.g., HepG2) are cultured in DMEM with 10% FBS. Cells are treated with VULM 1457 (0.1-50 uM) for 24-48 hours. Adrenomedullin (AM) levels in the culture medium are measured by ELISA. AM receptor expression (CRLR, RAMP2, RAMP3) is assessed by qPCR and Western blot. Cellular cholesterol content is measured by enzymatic colorimetric kits after lipid extraction. Cell viability is assessed by MTT assay.
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| Animal Protocol |
Animal/Disease Models: Male Wistar rats (250-300 g body weight), fed a standard diet and tap water ad libitum[2]
Doses: 50 mg/kg/day Route of Administration: Administered as an admixture to the fat-cholesterol diet for 5 days Experimental Results: Improved the overall myocardial ischaemia-reperfusion injury outcomes in the diabetic-hypercholesterolaemic rats by suppressing arrhythmogenesis as well as by reducing myocardial necrosis, aside from remarkable hypolipidaemic activity. Diabetic-hypercholesterolemic rats (e.g., streptozotocin-induced diabetic rats fed a high-cholesterol diet) are used. VULM 1457 is administered as an admixture to the fat-cholesterol diet (50 mg/kg/day) for 5 days. Plasma total cholesterol and triglycerides are measured by enzymatic assays. Myocardial ischemia-reperfusion (I/R) injury is induced by temporary ligation of the left anterior descending coronary artery, followed by reperfusion. Infarct size is measured by TTC staining, and arrhythmia incidence is recorded by ECG. Hamsters fed a high-cholesterol lipid diet are used for microcirculation studies: RBC velocity in paw microcirculation is measured by capillary microscopy. |
| ADME/Pharmacokinetics |
No specific pharmacokinetic data reported for VULM 1457. As a small molecule ACAT inhibitor, it is expected to be absorbed after oral administration, with metabolism in the liver via phase I (CYP450) and phase II enzymes. Excretion is likely via bile and urine. Oral bioavailability and half-life are not publicly available but can be inferred from chemical properties and structure-activity relationships.
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| Toxicity/Toxicokinetics |
No specific toxicity data reported for VULM 1457. As an ACAT inhibitor, it may influence lipid homeostasis across various tissues. In animal studies, it was administered at 50 mg/kg/day for 5 days without reported overt toxicity, suggesting a reasonable safety margin at therapeutic doses. Long-term safety studies are not publicly available.
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| References |
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| Additional Infomation |
VULM 1457 is a research tool for studying ACAT inhibition, adrenomedullin signaling, hypolipidemia, and myocardial ischemia-reperfusion injury. It has potential applications in diabetes and hypercholesterolemia research. It is not approved for clinical use. The compound is also referred to as an Acyl-CoA:cholesterol acyltransferase (ACAT) or SOAT inhibitor. References include publications on its hypolipidemic activity and cardioprotective effects in diabetic-hypercholesterolemic rats. The CAS number is 228544-65-8. Molecular formula: C25H27N3O3S. Molecular weight: 449.57. Solubility: <44.96 mg/mL in DMSO.
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| Molecular Formula |
C25H27N3O3S
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|---|---|
| Molecular Weight |
449.57
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| Exact Mass |
449.177
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| CAS # |
228544-65-8
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| PubChem CID |
9933427
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
8.306
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
592
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)C1=C(C(=CC=C1)C(C)C)NC(=O)NC2=CC=C(C=C2)SC3=CC=C(C=C3)[N+](=O)[O-]
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| InChi Key |
XFFITGBWVLQNCD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H27N3O3S/c1-16(2)22-6-5-7-23(17(3)4)24(22)27-25(29)26-18-8-12-20(13-9-18)32-21-14-10-19(11-15-21)28(30)31/h5-17H,1-4H3,(H2,26,27,29)
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| Chemical Name |
1-[2,6-di(propan-2-yl)phenyl]-3-[4-(4-nitrophenyl)sulfanylphenyl]urea
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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: 250 mg/mL (556.09 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2243 mL | 11.1217 mL | 22.2435 mL | |
| 5 mM | 0.4449 mL | 2.2243 mL | 4.4487 mL | |
| 10 mM | 0.2224 mL | 1.1122 mL | 2.2243 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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