| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
- Cytochrome P450 (CYP450) enzymes (metabolic targets): CYP3A4 (IC50 = 3.2 μM), CYP2D6 (IC50 = 8.5 μM), CYP2C9 (10 μM concentration: 42% inhibition rate), CYP2C19 (10 μM concentration: 38% inhibition rate), CYP1A2 (10 μM concentration: 25% inhibition rate) [1]
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| ln Vitro |
- Inhibition of CYP450 enzyme activity: Meranzin (hydrate) showed concentration-dependent inhibitory effects on human CYP450 enzymes in vitro. At 10 μM, it inhibited CYP3A4 (main metabolic enzyme), CYP2D6, CYP2C9, CYP2C19, and CYP1A2 by 72%, 58%, 42%, 38%, and 25%, respectively. Among them, it had the strongest inhibitory effect on CYP3A4 (IC50 = 3.2 μM), followed by CYP2D6 (IC50 = 8.5 μM) [1]
- Metabolic enzyme identification: In human liver microsomes, the metabolism of Meranzin (hydrate) was significantly inhibited by the CYP3A4-specific inhibitor ketoconazole (1 μM), reducing metabolite formation by 68%. This confirmed that CYP3A4 is the primary enzyme responsible for its in vitro metabolism [1] |
| ln Vivo |
- Anti-atherosclerotic effect in ApoE-/- mice: High-fat diet (HFD)-fed ApoE-/- mice were treated with Meranzin (hydrate) (10, 20 mg/kg, oral gavage, once daily for 12 weeks). Compared with the HFD model group:
- The 20 mg/kg group showed a 35% reduction in aortic atherosclerotic plaque area, a 28% decrease in serum total cholesterol (TC), and a 32% decrease in low-density lipoprotein cholesterol (LDL-C) [2] - Aortic tissue inflammation was alleviated: TNF-α and IL-6 protein levels were reduced by 42% and 38%, respectively, in the 20 mg/kg group [2] - Behavioral improvement in ApoE-/- mice: In the open field test, the 20 mg/kg Meranzin (hydrate) group showed a 45% increase in total movement distance and a 52% increase in central zone residence time compared with the model group. In the Morris water maze test, the escape latency was shortened by 38%, and the number of platform crossings was increased by 2.1-fold [2] - Activation of BDNF-TrkB pathway: In the 20 mg/kg group, Meranzin (hydrate) increased BDNF protein expression in the hippocampus by 2.1-fold and aortic tissue by 1.8-fold; the phosphorylation level of TrkB (p-TrkB) was upregulated by 2.3-fold (hippocampus) and 1.9-fold (aorta) [2] |
| Enzyme Assay |
- CYP450 enzyme activity assay (fluorescence-based): The reaction system (200 μL) contained 50 mM potassium phosphate buffer (pH 7.4), 1 mM NADPH (cofactor), human liver microsomes (0.5 mg/mL protein), CYP-specific fluorescent substrates (e.g., 7-benzyloxy-4-trifluoromethylcoumarin for CYP3A4), and different concentrations of Meranzin (hydrate) (0.1–50 μM). The system was incubated at 37°C for 30 min, and the reaction was terminated by adding 200 μL acetonitrile. After centrifugation at 12,000 × g for 10 min, the fluorescence intensity of the supernatant was measured (excitation wavelength: 405 nm, emission wavelength: 510 nm). Enzyme activity was calculated based on the fluorescence intensity of the product, and the inhibition rate and IC50 were determined by concentration-response curves [1]
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| Cell Assay |
- CYP3A4-overexpressing HEK293 cell assay: HEK293 cells stably expressing human CYP3A4 were cultured in DMEM medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin at 37°C in a 5% CO₂ incubator. Cells were seeded into 24-well plates at 2×10⁵ cells/well. When confluence reached 70%, Meranzin (hydrate) (0.5, 1, 5, 10 μM) was added, and the CYP3A4-specific substrate testosterone (10 μM) was co-incubated. After 24 h, the culture supernatant was collected, and the amount of testosterone metabolite (6β-hydroxytestosterone) was detected by high-performance liquid chromatography (HPLC) to evaluate the effect of Meranzin (hydrate) on CYP3A4 activity [1]
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| Animal Protocol |
- Animal grouping and model establishment: Male ApoE-/- mice (8 weeks old, 22–25 g) were randomly divided into 3 groups (n=8/group): 1) Normal control group (normal diet, no treatment); 2) HFD model group (HFD: 21% fat, 0.15% cholesterol, oral gavage of 0.5% carboxymethyl cellulose sodium (CMC-Na)); 3) Meranzin (hydrate) treatment groups (HFD + 10 mg/kg or 20 mg/kg Meranzin (hydrate), oral gavage) [2]
- Drug preparation and administration: Meranzin (hydrate) was dissolved in 0.5% CMC-Na to prepare 1 mg/mL and 2 mg/mL solutions. All groups were treated once daily for 12 weeks. Body weight was recorded weekly during the experiment [2] - Sample collection and detection: After 12 weeks, mice were euthanized. Serum was collected for TC and LDL-C detection (enzymatic method). Aortic tissue was harvested: one part was fixed in 4% paraformaldehyde for oil red O staining (to measure plaque area); another part was frozen in liquid nitrogen for Western blot (to detect TNF-α, IL-6, BDNF, TrkB, p-TrkB). Hippocampal tissue was collected for Western blot analysis of BDNF and p-TrkB [2] |
| ADME/Pharmacokinetics |
In vitro metabolism: Melanzin (hydrate) is mainly metabolized by human CYP3A4 in vitro. In human liver microsomes, when co-incubated with the CYP3A4 inhibitor ketoconazole (1 μM) and the CYP2D6 inhibitor quinidine (1 μM), the production of its major metabolite (M1) was reduced by 68% and 45%, respectively [1]. Metabolite profile: In human liver microsomes, after incubation of Melanzin (hydrate) (10 μM) for 60 minutes, two major metabolites (M1 and M2) were generated. M1 accounted for 72% of the total metabolites, and its structure was identified by mass spectrometry as a hydroxylated derivative [1].
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| References |
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| Additional Infomation |
8-[(2S)-2,3-dihydroxy-3-methylbutyl]-7-methoxychromene-2-one has been reported in Glycosmis pentaphylla, Ferula sumbul, and other organisms with relevant data. Background: Melanzin (hydrate) is a natural coumarin compound isolated from the traditional Chinese medicine formula Chaihu Shugan San. It is a potential antidepressant and has been found to have anti-atherosclerotic activity [1,2].
- Mechanism of action: 1) Metabolic mechanism: In vitro studies have shown that it is mainly metabolized by CYP3A4 and has a weak inhibitory effect on various CYP450 enzymes[1]; 2) Therapeutic mechanism: In high-fat diet (HFD) ApoE-/- mice, it exerts anti-atherosclerotic and neuroprotective effects by inhibiting inflammation (reducing TNF-α/IL-6 levels) and activating the BDNF-TrkB pathway[2] - Clinical significance: The inhibitory effect of melanin (hydrate) on CYP3A4 suggests that drug interactions may exist when used in combination with CYP3A4 substrates (such as certain statins). Its dual effects on atherosclerosis and behavior make it a candidate drug for the treatment of diseases with vascular and neurocognitive disorders[1,2] |
| Molecular Formula |
C15H18O5
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|---|---|
| Molecular Weight |
278.3004
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| Exact Mass |
278.115
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| CAS # |
5875-49-0
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| PubChem CID |
821434
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
500.5±50.0 °C at 760 mmHg
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| Melting Point |
130-131°C
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| Flash Point |
188.3±23.6 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.580
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| LogP |
0.61
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
20
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| Complexity |
390
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)([C@H](CC1=C(C=CC2=C1OC(=O)C=C2)OC)O)O
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| InChi Key |
KGGUASRIGLRPAX-LBPRGKRZSA-N
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| InChi Code |
InChI=1S/C15H18O5/c1-15(2,18)12(16)8-10-11(19-3)6-4-9-5-7-13(17)20-14(9)10/h4-7,12,16,18H,8H2,1-3H3/t12-/m0/s1
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| Chemical Name |
8-[(2S)-2,3-dihydroxy-3-methylbutyl]-7-methoxychromen-2-one
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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 and light. |
| 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 (~359.32 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 | 3.5932 mL | 17.9662 mL | 35.9324 mL | |
| 5 mM | 0.7186 mL | 3.5932 mL | 7.1865 mL | |
| 10 mM | 0.3593 mL | 1.7966 mL | 3.5932 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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