| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| Targets |
5β-Dihydrocortisone is not an active agonist but rather functions as a metabolite product. It is the product of the enzyme 5β-reductase (AKR1D1), a key enzyme involved in the metabolism of cortisol and cortisone in the liver. Research indicates that 5β-reductase plays an important role in regulating glucocorticoid availability and glucocorticoid receptor (GR) activation by reducing cortisone to 5β-dihydrocortisone. Unlike its 5α-reduced counterpart, 5β-dihydrocortisone exhibits significantly diminished binding to the glucocorticoid receptor and is generally considered biologically inactive with respect to glucocorticoid action.
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| ln Vitro |
5β-Dihydrocortisone itself does not exhibit significant in vitro pharmacological activity due to the lack of the Δ⁴-3-keto structure required for glucocorticoid receptor agonism. In in vitro studies, it is primarily used as a negative control or as a substrate/product for metabolic pathway studies. Compared to 5α-dihydrocortisone (which binds and activates the glucocorticoid receptor), 5β-dihydrocortisone shows significantly reduced binding to the glucocorticoid receptor and does not activate it. This stereochemical difference has profound implications for the molecule's three-dimensional structure and its ability to interact with steroid receptors.
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| ln Vivo |
In vivo, 5β-dihydrocortisone is one of the major inactive urinary metabolites of cortisone, generated through the A-ring reduction of cortisone and hydrocortisone catalyzed by the enzyme 5β-reductase (AKR1D1) in the liver and kidney. This compound is further conjugated with glucuronic acid and ultimately excreted in urine via the kidneys. In clinical studies, the urinary excretion levels of 5β-dihydrocortisone and its conjugates serve as markers for assessing the metabolic clearance rate of steroids in the body. Research has shown that AKR1D1 regulates glucocorticoid availability by generating 5β-dihydrocortisone.
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| Enzyme Assay |
In vitro assays to study the interaction of 5β-Dihydrocortisone with metabolic enzymes can employ recombinant human 5β-reductase (AKR1D1) activity assays. The brief protocol is as follows: Pre-incubate recombinantly expressed purified AKR1D1 enzyme protein with the cofactor NADPH (final concentration 100-200 μM) in reaction buffer at 37°C for 5 minutes. Subsequently, add serial concentrations (0.1-100 μM) of 5β-Dihydrocortisone as a substrate, or add cortisone as a substrate and detect the formation of 5β-Dihydrocortisone, in 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 enzyme kinetic parameters (Kₘ, Vₘₐₓ) or conversion rates.
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| Cell Assay |
5β-Dihydrocortisone can be used to study the regulation of steroid metabolic pathways in cells. A typical cellular assay protocol is as follows: Seed human hepatoma cells (e.g., HepG2) 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 in serum-free medium (prepare stock solution in DMSO, then dilute with culture medium to working concentration) 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 the formation of metabolites inside the cells or in the culture medium using LC-MS/MS. MTT or CCK-8 assays can be used to evaluate the impact of the compound on cell viability. Research has shown that 5β-reductase regulates glucocorticoid availability and GR activation in HepG2 cells.
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| Animal Protocol |
The application of 5β-Dihydrocortisone in in vivo animal experiments is primarily as a metabolite standard in pharmacokinetic (PK) studies. A typical experimental protocol is as follows: Use male SD rats (body weight 180-220 g), administer cortisone or cortisone acetate 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 24-hour urine samples. After centrifugation of blood samples to separate plasma, add internal standard for protein precipitation and liquid-liquid extraction; urine samples are analyzed after appropriate dilution. Quantify metabolites including 5β-Dihydrocortisone 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 |
5β-Dihydrocortisone is not a dosage form itself but rather an in vivo metabolite of cortisone. In vivo, after oral administration of cortisone, it undergoes hepatic first-pass metabolism and is reduced to 5β-Dihydrocortisone by the enzyme 5β-reductase (AKR1D1). The calculated LogP value of this compound is approximately 2.07, indicating certain lipophilic properties. Further metabolism of 5β-Dihydrocortisone involves conjugation with glucuronic acid to form water-soluble glucuronide conjugates, which are ultimately excreted in urine via the kidneys. In vitro, this compound has a solubility of 100 mg/mL (275.89 mM) in DMSO and can be formulated in vivo with vehicles such as 10% DMSO + 90% corn oil.
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| Toxicity/Toxicokinetics |
As an endogenous inactivated 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 complete absence of the Δ⁴-3-keto structure required for glucocorticoid activity, this compound cannot activate the glucocorticoid receptor and therefore does not cause the typical adverse reactions associated with glucocorticoid excess (such as immunosuppression, hyperglycemia, osteoporosis, etc.). In laboratory use, this compound is for research use only and should be handled following standard operating procedures (SOPs), avoiding inhalation, ingestion, or skin contact.
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| References |
[1]. AKR1D1 regulates glucocorticoid availability and glucocorticoid receptor activation in human hepatoma cells. J Steroid Biochem Mol Biol
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| Additional Infomation |
17,21-Dihydroxy-5β-pregnane-3,11,20-trione is a 4,5-dihydrocortisone with a β-configuration at the 5-position. It is a 3-oxo-5β-steroid, a primary α-hydroxy ketone, a tertiary α-hydroxy ketone, and also a 4,5-dihydrocortisone.
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| Molecular Formula |
C21H30O5
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|---|---|
| Molecular Weight |
362.46
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| Exact Mass |
362.209
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| CAS # |
68-54-2
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| PubChem CID |
65554
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.069
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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 |
2
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| Heavy Atom Count |
26
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| Complexity |
671
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| Defined Atom Stereocenter Count |
7
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| SMILES |
CC12CCC(=O)CC1CCC3C2C(=O)CC4(C3CCC4(C(=O)CO)O)C
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| InChi Key |
YCLWEYIBFOLMEM-FNLRALKVSA-N
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| InChi Code |
InChI=1S/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h12,14-15,18,22,26H,3-11H2,1-2H3/t12-,14+,15+,18-,19+,20+,21+/m1/s1
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| Chemical Name |
(5R,8S,9S,10S,13S,14S,17R)-17-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,4,5,6,7,8,9,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,11-dione
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| Synonyms |
4,5beta-Dihydrocortisone; RefChem:1069417; 5beta-Dihydrocortisone; 68-54-2; 5-Dihydrocortisone;
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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 (275.89 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7589 mL | 13.7946 mL | 27.5893 mL | |
| 5 mM | 0.5518 mL | 2.7589 mL | 5.5179 mL | |
| 10 mM | 0.2759 mL | 1.3795 mL | 2.7589 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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