| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
As a 5β-reduced metabolite of cortisone, this compound exhibits very low affinity for the glucocorticoid receptor (GR). The 5β-reduction is a major metabolic inactivation pathway for cortisone and hydrocortisone, where the C4-C5 double bond in ring A is saturated and converted to the 5β configuration, eliminating the Δ⁴-3-keto structure required for high-affinity binding to the glucocorticoid receptor. Therefore, unlike cortisone or hydrocortisone, 5β-Dihydrocortisone acetate does not possess significant direct glucocorticoid receptor agonist activity and is primarily excreted as a metabolic end product via urine and bile.
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|---|---|
| ln Vitro |
Independent in vitro activity studies on 5β-Dihydrocortisone acetate are relatively scarce, primarily because this compound is an inactivated metabolite of corticosteroids lacking significant pharmacological activity. Compared to the parent compound cortisone, this compound has lost the structural basis for glucocorticoid activity due to saturation of the Δ⁴-3-keto structure. In classical glucocorticoid activity evaluation systems, the activity of 5β-reduced metabolites is typically several orders of magnitude lower than that of their parent compounds. The primary activity of this compound lies in its use as a metabolic fingerprinting standard for identifying corticosteroid metabolic transformations in biological samples.
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| ln Vivo |
In vivo, 5β-Dihydrocortisone acetate, as one of the major metabolites of cortisone and hydrocortisone, does not possess significant anti-inflammatory or immunosuppressive activity. This compound is generated in the liver via reduction of the A-ring of corticosteroids by 5β-reductase (AKR1D1), followed by further conjugation with glucuronic acid or sulfate, and ultimately excretion via urine. In in vivo pharmacological studies, this compound is typically not used as an active drug but rather as an endpoint marker for metabolic studies, reflecting the body's clearance capacity for glucocorticoids and metabolic status.
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| Enzyme Assay |
In vitro methods to evaluate the interaction of 5β-Dihydrocortisone acetate as a substrate or metabolite with metabolic enzymes can employ recombinant human 5β-reductase (AKR1D1) or 11β-hydroxysteroid dehydrogenase (11β-HSD) activity assays. The brief protocol is as follows: Pre-incubate recombinantly expressed purified enzyme protein with NADPH or NAD⁺ (final concentration 100-200 μM) in reaction buffer at 37°C for 5 minutes, then initiate the reaction by adding serial concentrations (0.1-100 μM) of the test compound to a total reaction volume of 200 μL. After incubation at 37°C for 30-60 minutes, terminate the reaction by adding ice-cold acetonitrile, and centrifuge to remove protein precipitate. Analyze the supernatant using LC-MS/MS to quantify substrate consumption or product formation, and calculate the enzyme activity inhibition rate or conversion rate by comparison with control groups.
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| Cell Assay |
Due to the lack of direct glucocorticoid activity of 5β-Dihydrocortisone acetate, its application in cellular experiments is primarily focused on metabolic studies or as a negative control. A typical cellular assay protocol is as follows: Seed human hepatoma cells (e.g., HepG2) or human intestinal epithelial cells at a density of 5×10⁵ cells per well in 6-well plates and culture at 37°C in 5% CO₂ for 24 hours until adherence. Prepare serial concentrations (0.1-50 μM) of 5β-Dihydrocortisone acetate in serum-free medium and add to cells for 6-24 hours of treatment. Collect cell culture supernatant and cell lysate, purify via solid-phase extraction (SPE), and detect metabolite formation in cells or culture medium using LC-MS/MS. MTT or CCK-8 assays can be used to evaluate the impact of the compound on cell viability.
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| Animal Protocol |
The primary application of 5β-Dihydrocortisone acetate in in vivo animal experiments is as a metabolite standard or tracer in pharmacokinetic (PK) studies. A typical experimental protocol is as follows: Use male SD rats (body weight 180-220 g), administer cortisone or hydrocortisone via tail vein injection (1-5 mg/kg) or oral gavage (5-20 mg/kg), then collect blood samples into heparinized tubes at different time points (5, 15, 30, 60, 120, 240, 480 minutes), along with urine and feces. After centrifugation of blood samples to separate plasma, add internal standard for protein precipitation and liquid-liquid extraction; urine samples are directly analyzed after appropriate dilution. Quantify metabolites including 5β-Dihydrocortisone acetate using validated LC-MS/MS methods, plot plasma concentration-time curves of the parent drug and its metabolites, and calculate pharmacokinetic parameters.
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| ADME/Pharmacokinetics |
As a metabolite of cortisone, the in vivo exposure level of 5β-Dihydrocortisone acetate primarily depends on the metabolic rate of the precursor drug. This compound is generated by catalysis of 5β-reductase (AKR1D1) in the liver and kidney, which plays a critical role in the A-ring reduction of cortisone and hydrocortisone. In vitro experimental data indicate that the calculated LogP value of this compound is approximately 2.69, suggesting certain lipophilic properties. This compound is further converted into water-soluble conjugates catalyzed by UDP-glucuronosyltransferase (UGT) or sulfotransferase (SULT), and ultimately excreted via urine through the kidneys, with a small amount excreted as the unchanged form via bile into feces.
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| Toxicity/Toxicokinetics |
As an endogenous metabolite of cortisone and hydrocortisone, this compound is present in the human body under normal physiological conditions and is generally not considered to have significant toxicity. Due to the absence of the Δ⁴-3-keto structure, this compound cannot effectively activate the glucocorticoid receptor and therefore does not cause the typical adverse reactions associated with glucocorticoid excess (such as Cushing's syndrome, hyperglycemia, immunosuppression, etc.). In laboratory use, this compound should be handled following standard operating procedures (SOP) as a chemical reagent, avoiding inhalation, ingestion, or skin contact.
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| References |
[1]. A novel synthesis of tetrahydrocortisone 3-glucuronide. Journal of Carbohydrate Chemistry. 2022, 41(1):18-27.
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| Molecular Formula |
C23H32O6
|
|---|---|
| Molecular Weight |
404.49658
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| Exact Mass |
404.22
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| CAS # |
1499-59-8
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| PubChem CID |
229293
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.224g/cm3
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| Boiling Point |
556.1ºC at 760mmHg
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| Flash Point |
187.9ºC
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| Vapour Pressure |
1.11E-14mmHg at 25°C
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| Index of Refraction |
1.54
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| LogP |
2.64
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
773
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| Defined Atom Stereocenter Count |
7
|
| SMILES |
CC(OCC([C@]1(CC[C@H]2[C@@H]3CC[C@@H]4CC(CC[C@]4(C)[C@H]3C(C[C@]12C)=O)=O)O)=O)=O
|
| InChi Key |
AZCNJEFLSOQGST-LPEMZKRWSA-N
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| InChi Code |
InChI=1S/C23H32O6/c1-13(24)29-12-19(27)23(28)9-7-17-16-5-4-14-10-15(25)6-8-21(14,2)20(16)18(26)11-22(17,23)3/h14,16-17,20,28H,4-12H2,1-3H3/t14-,16+,17+,20-,21+,22+,23+/m1/s1
|
| Chemical Name |
[2-[(5R,8S,9S,10S,13S,14S,17R)-17-hydroxy-10,13-dimethyl-3,11-dioxo-1,2,4,5,6,7,8,9,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] acetate
|
| Synonyms |
Dihydrocortisone acetate; 1499-59-8; 5b-Dihydrocortisone Acetate 21-Acetate; 5beta-Dihydrocortisone acetate 21-acetate; [2-[(5R,8S,9S,10S,13S,14S,17R)-17-hydroxy-10,13-dimethyl-3,11-dioxo-1,2,4,5,6,7,8,9,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] acetate;
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.4722 mL | 12.3609 mL | 24.7219 mL | |
| 5 mM | 0.4944 mL | 2.4722 mL | 4.9444 mL | |
| 10 mM | 0.2472 mL | 1.2361 mL | 2.4722 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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