| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
CYP3A4
Cytochrome P450 3A4 (CYP3A4); mechanism-based (suicide) inhibitor. |
|---|---|
| ln Vitro |
6',7'-DHB is a potent, irreversible inhibitor of CYP3A4 with an IC50 of approximately 25 microM. It preferentially and irreversibly inhibits intestinal CYP3A4, which is responsible for the well-known "grapefruit juice effect" leading to increased oral bioavailability of many drugs. It is more potent than bergamottin and acts as a suicide inhibitor by binding covalently to the enzyme.
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| Enzyme Assay |
The standard CYP3A4 inhibition assay uses pooled human liver microsomes or recombinant CYP3A4 enzyme. The assay mixture contains compound, enzyme, NADPH, and a specific CYP3A4 fluorogenic substrate (e.g., dibenzylfluorescein or midazolam). Pre-incubation with NADPH is critical to observe the mechanism-based inhibition. After incubation, the formation of the fluorescent or LC-MS-detectable metabolite is measured to determine IC50 values.
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| Cell Assay |
Human hepatocytes can be used to assess the compound's ability to inhibit cellular CYP3A4 activity in a more physiologically relevant context. Primary hepatocytes are treated with 6',7'-DHB, and then a CYP3A4 probe substrate (e.g., midazolam) is added. The rate of metabolite formation (e.g., 1'-hydroxymidazolam) is measured by LC-MS to assess functional enzyme inhibition.
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| Animal Protocol |
The in vivo effect of 6',7'-DHB is studied in dogs or rats, often using oral administration of the compound followed by a CYP3A4 probe drug like triazolam. The compound increases the oral bioavailability of the probe drug by inhibiting intestinal CYP3A4-mediated first-pass metabolism. Blood samples are collected to compare the pharmacokinetic profiles.
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| ADME/Pharmacokinetics |
As a dietary furanocoumarin, 6',7'-DHB has low oral bioavailability itself due to extensive metabolism. It acts locally in the gut wall. It is rapidly absorbed but undergoes significant first-pass metabolism. Its primary pharmacological effect is as a potent inactivator of CYP3A4, leading to systemic drug-drug interactions with co-administered CYP3A4 substrates.
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| Toxicity/Toxicokinetics |
Toxicity Summary
Many furanocoumarins act through mechanisms based on their ability to form photoadducts with DNA and other cellular components, such as RNA, proteins, and various membrane proteins, including phospholipases A2 and C, calcium-dependent and cAMP-dependent protein kinases, and epidermal growth factor. Furanocoumarins can intercalate between DNA base pairs and form cycloadducts upon UVA irradiation (L579). 6,7-Dihydroxybergamotin also acts as a CYP3A4 inhibitor (A3109). This compound is a natural dietary component generally recognized as safe (GRAS) as part of grapefruit juice. However, in combination with CYP3A4 substrates, it can cause significant adverse drug reactions due to increased drug exposure. There are no dedicated toxicology studies for the isolated compound for use as a drug candidate. |
| References | |
| Additional Infomation |
6',7'-Dihydroxybergamotin is a type of psoralen compound.
This compound is a research chemical, not an approved drug. It is the primary active ingredient responsible for the grapefruit juice-drug interaction phenomenon and is widely used as a research tool to study CYP3A4-mediated metabolism and drug interactions. It helps in understanding intestinal drug metabolism and predicting clinical food-drug interactions. |
| Molecular Formula |
C21H24O6
|
|---|---|
| Molecular Weight |
372.41
|
| Exact Mass |
370.141
|
| CAS # |
145414-76-2
|
| Related CAS # |
(R)-6',7'-Dihydroxybergamottin;264234-05-1
|
| PubChem CID |
6440498
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
611.3±55.0 °C at 760 mmHg
|
| Melting Point |
112-113 °C
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| Flash Point |
323.5±31.5 °C
|
| Vapour Pressure |
0.0±1.8 mmHg at 25°C
|
| Index of Refraction |
1.633
|
| LogP |
5.57
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
27
|
| Complexity |
596
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C/C(=C\COC1=C2C=CC(=O)OC2=CC3=C1C=CO3)/CCC(C(C)(C)O)O
|
| InChi Key |
IXZUPBUEKFXTSD-MDWZMJQESA-N
|
| InChi Code |
InChI=1S/C21H24O6/c1-13(4-6-18(22)21(2,3)24)8-10-26-20-14-5-7-19(23)27-17(14)12-16-15(20)9-11-25-16/h5,7-9,11-12,18,22,24H,4,6,10H2,1-3H3/b13-8+
|
| Chemical Name |
4-[(E)-6,7-dihydroxy-3,7-dimethyloct-2-enoxy]furo[3,2-g]chromen-7-one
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6852 mL | 13.4261 mL | 26.8521 mL | |
| 5 mM | 0.5370 mL | 2.6852 mL | 5.3704 mL | |
| 10 mM | 0.2685 mL | 1.3426 mL | 2.6852 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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