| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
Beauvericin inhibits acyl-CoA: cholesterol acyltransferase (ACAT) [EC 2.3.1.26], an enzyme that catalyzes the conversion of cellular cholesterol and long-chain fatty acyl-CoA to cholesteryl ester [1].
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| ln Vitro |
In an enzyme assay using rat liver microsomes, beauvericin inhibited ACAT activity in a dose-dependent manner with an IC₅₀ value of 3.0 μM. Under the same conditions, the synthetic ACAT inhibitors CL 283,546 and CL 277,082 showed IC₅₀ values of 1.3 μM and 6.6 μM, respectively [1].
Beauvericin demonstrated more potent ACAT inhibitory activity than the seven enniatins tested (A, A1, B, B1, D, E, and F), which had IC₅₀ values ranging from 22 to 110 μM in the same enzyme assay [1]. The hydrophobicity of beauvericin (retention time of 12.0 minutes on ODS-HPLC) was between that of enniatin B1 (10.8 minutes) and enniatin E (12.5 minutes), indicating it is not as hydrophobic as some enniatins [1]. |
| Enzyme Assay |
ACAT activity was measured using rat liver microsomes as the enzyme source. The reaction mixture contained 0.1 M sodium phosphate buffer (pH 7.4), 100-200 μg microsomal protein, 300 μM BSA, 30 μM [1-¹⁴C]oleoyl-CoA (0.02 μCi), and a dispersion of cholesterol in Triton WR-1339 (20 μg cholesterol and 600 μg Triton WR-1339) in a total volume of 0.2 ml. The cholesterol dispersion was prepared by the method of Billheimer et al. The assay medium was preincubated for 30 minutes at 37°C, and the reaction was initiated by adding [1-¹⁴C]oleoyl-CoA. After 30 minutes of incubation, the reaction was stopped by adding 1.2 ml of chloroform-methanol (1:2). Lipid extracts were prepared according to the Folch method. Cholesteryl ester was isolated by thin layer chromatography (TLC) on silica gel 60 plates using a petroleum ether-diethyl ether-acetic acid (90:10:1) solvent system. The distribution of radioactivity on TLC was analyzed with a radioscanner to determine the amount of cholesteryl [¹⁴C]oleate [1].
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| Cell Assay |
J774 macrophages were maintained in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum and penicillin-streptomycin solution (50 units/ml benzylpenicillin and 50 μg/ml streptomycin). Two-day cultured J774 macrophages were collected by centrifugation (800 rpm, 5 minutes) and resuspended in growth medium at 1.0 × 10⁶ cells/ml. Then 0.74 ml of cell suspension was transferred into each well of 24-well microplates. After 2-hour incubation, the medium was changed to the same volume of FBS-free growth medium. Lipid dispersions with molar ratios of free cholesterol/phosphatidylcholine greater than 2 were prepared by sonication. [¹⁴C]oleic acid (0.25 μCi in 10 μl of 50% aqueous ethanol) and various concentrations of beauvericin (dissolved in 10 μl of ethanol) were added to each well. Cells were incubated at 37°C for 24 hours in a humidified incubator (95% air-5% CO₂). After incubation, 800 μl of 0.1% SDS in PBS was added to each well. Lipids were extracted and separated on TLC as described above. Beauvericin inhibited cholesteryl ester formation in a dose-dependent manner with an IC₅₀ value of 0.17 μM in J774 macrophages [1].
Cell viability was determined by the trypan blue dye exclusion method following 24-hour incubation of J774 cells in FBS-free growth medium with the lipid dispersion and in the presence or absence of different concentrations of beauvericin. The CD₅₀ (drug concentration causing 50% cell damage) for beauvericin was approximately 10 μM, giving a CD₅₀/IC₅₀ ratio of 65 [1]. In mouse peritoneal macrophages, beauvericin showed similar effects with high specificity (CD₅₀/IC₅₀ ratio >130). Triacylglycerol formation was enhanced about 1.5-fold at drug concentrations where cholesteryl ester formation was inhibited [1]. |
| Toxicity/Toxicokinetics |
In J774 macrophages, beauvericin showed a CD₅₀ (drug concentration causing 50% cell damage) of approximately 10 μM. This resulted in a CD₅₀/IC₅₀ ratio of 65, indicating high specificity for ACAT inhibition compared to other cyclodepsipeptides tested [1].
In mouse peritoneal macrophages, beauvericin showed even higher specificity with a CD₅₀/IC₅₀ ratio greater than 130 [1]. Beauvericin was less cytotoxic than the more hydrophobic enniatins (A, F, A1, and E), which had CD₅₀ values of 2.6 to 2.9 μM in J774 macrophages [1]. At concentrations where cholesteryl ester formation was inhibited, beauvericin enhanced triacylglycerol formation 1.5- to 4-fold in J774 macrophages and about 1.5-fold in mouse peritoneal macrophages [1]. |
| References | |
| Additional Infomation |
Bovidiacin is a trimeric cyclic peptide composed of alternating methylphenylalanine and hydroxyvalerate residues. It possesses multiple functions, including as a fungicide, antibiotic insecticide, apoptosis inhibitor, fungal metabolite, ion carrier, antifungal agent, P450 inhibitor, and antitumor agent. Bovidiacin has been reported in Fusarium oxysporum, Fusarium tumefaciens, and other organisms with relevant data. Bovidiacin is a cyclic hexapeptide antibiotic and fungicide isolated from Beauveria bassiana and various Fusarium species. As a potassium-specific ion carrier, bovidiacin A increases intracellular calcium ion concentration and induces DNA fragmentation and apoptosis through a calcium-dependent caspase 3-sensitive pathway. This compound has been investigated as a potential antitumor agent. (NCI04)
Beauvericin is a cyclodepsipeptide antibiotic produced by fungal strains such as Fusarium sp. FO-740. It was originally reported as an antifungal and insecticidal antibiotic [1]. Structurally, beauvericin contains L-phenylalanine, unlike the enniatins which contain branched alkyl amino acids. This aromatic group may contribute to its ACAT inhibitory activity [1]. Beauvericin is one of the most potent ACAT inhibitors of microbial origin identified to date, with an IC₅₀ of 3.0 μM in an enzyme assay using rat liver microsomes [1]. The ACAT inhibitory activity of beauvericin appears to be independent of its ionophoric activity, as it showed more potent inhibition than more hydrophobic enniatins and demonstrated high specificity in cell-based assays [1]. A correlation was observed between hydrophobicity and ACAT inhibitory activity for enniatins, but beauvericin did not follow this pattern, suggesting a possible specific interaction with ACAT [1]. |
| Molecular Formula |
C45H57N3O9
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|---|---|
| Molecular Weight |
783.94900
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| Exact Mass |
783.409
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| CAS # |
26048-05-5
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| PubChem CID |
3007984
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
975.6±65.0 °C at 760 mmHg
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| Melting Point |
93-94℃
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| Flash Point |
543.8±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.530
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| LogP |
5.49
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
57
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| Complexity |
1200
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| Defined Atom Stereocenter Count |
6
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| SMILES |
CC(C)[C@@H]1C(=O)N([C@H](C(=O)O[C@@H](C(=O)N([C@H](C(=O)O[C@@H](C(=O)N([C@H](C(=O)O1)CC2=CC=CC=C2)C)C(C)C)CC3=CC=CC=C3)C)C(C)C)CC4=CC=CC=C4)C
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| InChi Key |
GYSCAQFHASJXRS-FFCOJMSVSA-N
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| InChi Code |
InChI=1S/C45H57N3O9/c1-28(2)37-40(49)46(7)35(26-32-21-15-11-16-22-32)44(53)56-39(30(5)6)42(51)48(9)36(27-33-23-17-12-18-24-33)45(54)57-38(29(3)4)41(50)47(8)34(43(52)55-37)25-31-19-13-10-14-20-31/h10-24,28-30,34-39H,25-27H2,1-9H3/t34-,35-,36-,37+,38+,39+/m0/s1
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| Chemical Name |
(3S,6R,9S,12R,15S,18R)-3,9,15-tribenzyl-4,10,16-trimethyl-6,12,18-tri(propan-2-yl)-1,7,13-trioxa-4,10,16-triazacyclooctadecane-2,5,8,11,14,17-hexone
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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 (~127.56 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 | 1.2756 mL | 6.3780 mL | 12.7559 mL | |
| 5 mM | 0.2551 mL | 1.2756 mL | 2.5512 mL | |
| 10 mM | 0.1276 mL | 0.6378 mL | 1.2756 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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