| Size | Price | Stock | Qty |
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| 5mg |
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| 100mg | |||
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| Targets |
As a 5β-reduced metabolite, tetrahydrocortisone does not possess significant agonistic activity at the glucocorticoid receptor (GR). Research has shown that 5β-reduced metabolites bind to GR with much weaker affinity compared to 5α-reduced metabolites, with dissociation constants (Kd) in the micromolar rather than nanomolar range. Tetrahydrocortisone primarily participates in metabolism as the product of AKR1D1 (5β-reductase), an enzyme that regulates glucocorticoid availability and GR activation by reducing glucocorticoids to 5β-tetrahydro metabolites. Unlike 5α-reduced metabolites, 5β-tetrahydrocortisone cannot effectively bind to and activate GR due to the cis-configuration of its A/B ring junction.
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| ln Vitro |
Tetrahydrocortisone itself does not possess significant pharmacological activity in vitro. As a 5β-reduced metabolite, it stands in sharp contrast to 5α-reduced metabolites: studies have shown that 5α-tetrahydro metabolites (such as 5α-tetrahydrocorticosterone) effectively bind to and activate GR, whereas 5β-tetrahydro metabolites exhibit very low affinity for GR. In vitro, 5β-reduced metabolites poorly compete with dexamethasone for GR binding sites at nanomolar concentrations, with Kd values typically in the micromolar range, approximately 10 to 30 times higher than those of 5α-metabolites. Therefore, tetrahydrocortisone is not considered an agonist or antagonist in conventional GR activity assays.
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| ln Vivo |
Tetrahydrocortisone is one of the major terminal products of glucocorticoid inactivation metabolism in vivo. A classic 1968 human study showed that after intravenous injection of ³H-labeled tetrahydrocortisone, approximately 81% of radioactivity was recovered in urine within 48 hours, with the principal excretory product being tetrahydrocortisone itself (approximately half of the glucuronide fraction), along with its conversion product β-cortolone (12-31%). The study also found that approximately 20% of urinary tetrahydrocortisol originated from the reduction of tetrahydrocortisone. In clinical research, the urinary ratio of tetrahydrocortisone (THE) to tetrahydrocortisol (THF) is widely used as a biomarker to assess 11β-hydroxysteroid dehydrogenase (11β-HSD) activity and the metabolic status of glucocorticoids in vivo.
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| Enzyme Assay |
The classic method for determining the binding affinity of tetrahydrocortisone for the glucocorticoid receptor employs a radioligand competitive binding assay. The brief protocol is as follows: Prepare cytosol or membrane homogenates from rat hepatocytes or cell lines expressing human GR. Mix a fixed concentration of radiolabeled ligand (e.g., ³H-dexamethasone, approximately 1-10 nM) with serial dilutions of tetrahydrocortisone (concentration range 10⁻¹⁰ to 10⁻⁵ M), add the receptor protein, and incubate at 4°C for 12-24 hours to reach equilibrium. After incubation, adsorb unbound free ligand using dextran-coated charcoal (DCC) suspension, centrifuge at high speed, and measure radioactivity in the supernatant using a liquid scintillation counter. Generate a competition binding curve by nonlinear regression analysis to calculate the IC₅₀ (concentration required to inhibit 50% of radioligand binding), and convert to the inhibition constant (Ki) using the Cheng-Prusoff equation.
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| Cell Assay |
In cellular studies, the metabolic transformation of tetrahydrocortisone can be assessed using human hepatoma cell lines such as HepG2. A typical protocol is as follows: Seed HepG2 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 (1-50 μM) of tetrahydrocortisone 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 cells or in 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 |
Tetrahydrocortisone is primarily used as a metabolite marker in animal studies, with its in vivo generation studied following administration of precursor drugs. A typical experimental protocol is as follows: Use male SD rats (body weight 180-220 g), administer hydrocortisone or cortisone acetate via tail vein injection (1-5 mg/kg) or oral gavage (5-20 mg/kg), then collect blood samples at various time points (0, 1, 2, 4, 8, 12, 24 hours), along with 24-hour urine samples. Plasma is separated by centrifugation and purified by solid-phase extraction; urine samples are directly analyzed after appropriate dilution. Quantify metabolites including tetrahydrocortisone using validated LC-MS/MS methods, plot time-concentration curves, and calculate pharmacokinetic parameters. In a three-dimensional human liver bioreactor model, following hydrocortisone (100 nM) circulation for 2 days, Phase I metabolit
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| ADME/Pharmacokinetics |
Tetrahydrocortisone is not an active drug administered directly but rather a terminal metabolite of glucocorticoid metabolism in vivo. In humans, hydrocortisone is metabolized in the liver to tetrahydrocortisone via sequential action of 5β-reductase (AKR1D1) and 3α-hydroxysteroid dehydrogenase; this compound is subsequently conjugated with glucuronic acid to form tetrahydrocortisone-3-glucuronide, ultimately excreted in urine via the kidneys. In a three-dimensional human liver bioreactor model, the half-life of hydrocortisone was 23.03 hours with an elimination rate constant of 0.03 hour⁻¹; Phase I metabolites including tetrahydrocortisone accounted for 8-10% of drug loss, while Phase II metabolites (including glucuronides of tetrahydrocortisol and tetrahydrocortisone) accounted for 45-52%. The calculated LogP value of tetrahydrocortisone is approximately 2.1, indicating moderate lipophilicity.
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| Toxicity/Toxicokinetics |
As an endogenous inactivated metabolite of cortisone and hydrocortisone, this compound is present in human blood and urine 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 and the cis-configuration of its A/B ring junction, 5β-tetrahydrocortisone cannot effectively 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, avoiding inhalation, ingestion, or skin contact.
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| References | |
| Additional Infomation |
Urocortisone is a 21-hydroxysteroid.
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| Molecular Formula |
C21H32O5
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|---|---|
| Molecular Weight |
364.47578
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| Exact Mass |
364.225
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| Elemental Analysis |
C, 69.20; H, 8.85; O, 21.95
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| CAS # |
53-05-4
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| Related CAS # |
Tetrahydrocortisone-d5;Tetrahydrocortisone-d6;Tetrahydrocortisone acetate;17736-20-8
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| PubChem CID |
5866
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| Appearance |
White to off-white solid powder
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| Density |
1.249g/cm3
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| Boiling Point |
544.5ºC at 760mmHg
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| Melting Point |
190°C
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| Flash Point |
297.1ºC
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| Index of Refraction |
1.569
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| LogP |
1.861
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| Hydrogen Bond Donor Count |
3
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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 |
632
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| Defined Atom Stereocenter Count |
8
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| SMILES |
C[C@]12CC[C@H](C[C@H]1CC[C@@H]3[C@@H]2C(=O)C[C@]4([C@H]3CC[C@@]4(C(=O)CO)O)C)O
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| InChi Key |
SYGWGHVTLUBCEM-ZIZPXRJBSA-N
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| InChi Code |
InChI=1S/C21H32O5/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/h12-15,18,22-23,26H,3-11H2,1-2H3/t12-,13-,14+,15+,18-,19+,20+,21+/m1/s1
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| Chemical Name |
(3R,5R,8S,9S,10S,13S,14S,17R)-3,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,3,4,5,6,7,8,9,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-11-one
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| Synonyms |
TETRAHYDROCORTISONE; Urocortisone; 53-05-4; 5HF9TM2D15; NSC-76984; .
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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 : ~50 mg/mL (~137.18 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (3.43 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 12.5 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. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (3.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7436 mL | 13.7182 mL | 27.4363 mL | |
| 5 mM | 0.5487 mL | 2.7436 mL | 5.4873 mL | |
| 10 mM | 0.2744 mL | 1.3718 mL | 2.7436 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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