| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Mineralocorticoid receptor (MR), GABAA receptor, and angiostatic pathways. As a cortisol metabolite, Allotetrahydrocortisol has significantly reduced activity at the glucocorticoid receptor. However, it can interact with the mineralocorticoid receptor, potentially contributing to sodium retention. Additionally, it has been identified as a neuroactive steroid that modulates GABAA receptor activity, reducing GABA-mediated chloride ion uptake. It also exhibits angiostatic properties, inhibiting angiogenesis in the presence of non-anticoagulant heparin.
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| ln Vitro |
Tetrahydrocortisol, also known as 5a-tetrahydrocortisol, is an innate C21 steroid that originates from animals and has an axial 3-hydroxyl structure [1].
In vitro studies have demonstrated that Allotetrahydrocortisol is a natural C21 steroid with axial configuration of its 3-hydroxyl group, which dictates its specific receptor interactions. In rat cortical microsac preparations, both Allotetrahydrocortisol and its isomers reduce GABA-mediated chloride ion uptake, indicating a functional interaction with the GABAA receptor. As an angiostatic steroid, it is potent enough to influence capillary basement membrane turnover, though specific IC₅0 values for in vitro angiogenesis inhibition are not standardly reported. |
| ln Vivo |
In vivo, Allotetrahydrocortisol is not administered as a drug. Its role is as a metabolite. Elevated urinary ratios of (THF + 5alpha-THF)/THE (tetrahydrocortisone) are used as a diagnostic biomarker for Apparent Mineralocorticoid Excess (AME) syndrome, a condition caused by a deficiency in the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) enzyme. This accumulation of cortisol metabolites in urine is the primary evidence of its in vivo relevance. No therapeutic in vivo studies are performed.
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| Enzyme Assay |
A competitive ELISA or LC-MS/MS assay is used for quantification. For ELISA, a sample (urine or plasma) containing Allotetrahydrocortisol is added to a 96-well plate pre-coated with cortisol-specific antibodies (but cross-reactive with metabolites). A cortisol conjugate labeled with HRP is added. After incubation, the plate is washed and a substrate (TMB) is added. The reaction is stopped, and absorbance is measured at 450 nm. For LC-MS/MS, samples are extracted by solid-phase extraction (SPE) and injected into a C18 column coupled to a triple quadrupole mass spectrometer in MRM mode.
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| Cell Assay |
To study GABAA receptor function, primary rat cortical neurons or microsacs (membrane preparations) are isolated and pre-incubated with Allotetrahydrocortisol (e.g., 0.1-10 microM). [3H]-Flunitrazepam or [3⁵S]-TBPS is added to measure allosteric modulation. For chloride flux, a fluorescent dye sensitive to chloride ions (e.g., MQAE or YFP-based biosensor) is used. Cells are loaded with the dye, and changes in fluorescence are measured after the addition of GABA in the presence of the metabolite using a fluorescence plate reader.
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| Animal Protocol |
A standard LC-MS/MS protocol for human urine is used. A 1 mL urine sample is spiked with isotope-labeled internal standard (d4-Allotetrahydrocortisol). The sample undergoes enzymatic hydrolysis (beta-glucuronidase) to deconjugate the glucuronidated metabolites. It is then purified by solid-phase extraction (SPE) on a C18 column. The eluent is dried under nitrogen and reconstituted in mobile phase. The sample is injected into a UPLC system coupled with a tandem mass spectrometer (MS/MS) operated in negative ion electrospray mode. Multiple reaction monitoring (MRM) transitions specific for the compound is used.
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| ADME/Pharmacokinetics |
Allotetrahydrocortisol is an endogenous metabolite, not a xenobiotic. Therefore, traditional PK properties are not applicable. Its concentration in human urine varies but is typically in the range of 500-1500 microg/24h. In plasma, the half-life reflects the metabolic clearance of cortisol. It circulates bound to CBG (corticosteroid-binding globulin) and albumin. The compound is not orally bioavailable in the sense of a drug; it is simply absorbed from filtered plasma into the urine. It is soluble in DMSO, and its molecular weight is 366.49 g/mol.
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| Toxicity/Toxicokinetics |
Allotetrahydrocortisol is an endogenous, naturally produced steroid. It is not considered a drug and has no conventional toxicological profile. Elevated levels of this metabolite in diseases like AME syndrome are associated with hypertension, hypernatremia, and hypokalemia due to its mineralocorticoid activity. There is no known acute toxicity associated with the compound itself when used as a standard in research, as it is a component of normal human metabolism.
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| References | |
| Additional Infomation |
5α-Tetrahydrocortisol is a corticosteroid hormone.
Allotetrahydrocortisol is a certified reference standard (CRS) and biochemical. It is used as a marker to diagnose Apparent Mineralocorticoid Excess (AME) and as a tool in neuroendocrinology. It is not an investigational drug, and has not entered clinical trials or been approved for therapy. It is also known as 5alpha-THF, Kendall‘s Compound C, and Reichstein's Substance C. It is used in metabolomics research to study steroidogenesis and hormonal imbalances. It is classified as a steroid impurity in pharmaceutical analysis. |
| Molecular Formula |
C21H34O5
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|---|---|
| Molecular Weight |
366.49166
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| Exact Mass |
366.241
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| CAS # |
302-91-0
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| Related CAS # |
Allotetrahydrocortisol-d5;2687961-06-2
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| PubChem CID |
92748
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| Appearance |
White to off-white solid powder
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| Density |
1.253g/cm3
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| Boiling Point |
545.1ºC at 760mmHg
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| Melting Point |
244.5ºC
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| Flash Point |
297.6ºC
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| Index of Refraction |
1.579
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| LogP |
1.653
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| Hydrogen Bond Donor Count |
4
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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 |
593
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| Defined Atom Stereocenter Count |
9
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| SMILES |
C[C@]12CC[C@H](C[C@@H]1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@]4(C(=O)CO)O)C)O)O
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| InChi Key |
AODPIQQILQLWGS-FDSHTENPSA-N
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| InChi Code |
InChI=1S/C21H34O5/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/h12-16,18,22-24,26H,3-11H2,1-2H3/t12-,13+,14-,15-,16-,18+,19-,20-,21-/m0/s1
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| Chemical Name |
2-hydroxy-1-[(3R,5S,8S,9S,10S,11S,13S,14S,17R)-3,11,17-trihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-yl]ethanone
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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. |
| 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 | 2.7286 mL | 13.6429 mL | 27.2859 mL | |
| 5 mM | 0.5457 mL | 2.7286 mL | 5.4572 mL | |
| 10 mM | 0.2729 mL | 1.3643 mL | 2.7286 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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