| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
21-Acetoxypregnenolone targets the glucocorticoid receptor (GR, NR3C1) and may also modulate the NF-kappaB signaling pathway. As a pregnenolone derivative, it binds to the glucocorticoid receptor, although its affinity is lower than that of cortisol or dexamethasone. Upon binding, it translocates to the nucleus and suppresses the transcription of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6, IL-1beta) by antagonizing NF-kappaB activity. The compound also inhibits phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2), reducing the production of prostaglandins and leukotrienes. Unlike classical glucocorticoids, 21-acetoxypregnenolone is expected to have a milder side effect profile, with less impact on glucose metabolism and bone density. The compound is also a derivative of pregnenolone, which is a neurosteroid.
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| ln Vitro |
In vitro, 21-Acetoxypregnenolone exhibits anti-inflammatory activity. In LPS-stimulated RAW 264.7 macrophages, treatment with 21-acetoxypregnenolone (1-100 uM) reduces the production of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines (TNF-alpha, IL-6) in a concentration-dependent manner. The compound inhibits the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels, as assessed by Western blotting and qRT-PCR. It also suppresses the activation of NF-kappaB (p65 translocation) and MAPK (p38, ERK) signaling pathways. The IC₅0 for inhibition of NO production is in the range of 10-30 uM. The compound shows no significant cytotoxicity in RAW 264.7 cells at concentrations up to 100 uM, as determined by MTT assay.
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| ln Vivo |
In vivo, 21-Acetoxypregnenolone has been investigated in animal models of rheumatoid arthritis (RA). In the adjuvant-induced arthritis (AIA) rat model, administration of 21-acetoxypregnenolone (10-50 mg/kg, oral or intraperitoneal) reduces paw swelling and joint inflammation. Histological analysis of ankle joints shows reduced synovitis, pannus formation, and cartilage destruction. The compound also reduces serum levels of inflammatory markers (C-reactive protein, TNF-alpha, IL-6). In a carrageenan-induced paw edema model in rats, 21-acetoxypregnenolone (25-100 mg/kg, oral) produces a dose-dependent reduction in paw swelling, comparable to indomethacin (10 mg/kg). Unlike traditional non-steroidal anti-inflammatory drugs (NSAIDs), 21-acetoxypregnenolone does not cause gastric mucosal damage in rats at effective doses. It may be used in research on rheumatoid arthritis.
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| Enzyme Assay |
In vitro glucocorticoid receptor (GR) binding assay: To assess binding affinity, GR protein (from rat or human) is incubated with [3H]-dexamethasone (1-10 nM) and varying concentrations of 21-Acetoxypregnenolone (0.1-1000 uM) in binding buffer (10 mM Tris-HCl pH 7.4, 10% glycerol, 1 mM EDTA, 10 mM Na2MoO4, 1 mM DTT) at 4degC for 16-20 h. Bound radioligand is separated from free using dextran-coated charcoal, and radioactivity is counted. IC₅0 is calculated, and Ki is determined using the Cheng-Prusoff equation. For NF-kappaB inhibition assays, RAW 264.7 macrophages are transiently transfected with an NF-kappaB-luciferase reporter plasmid. After 24 h, cells are pre-treated with 21-Acetoxypregnenolone (1-100 uM) for 1 h, then stimulated with LPS (1 ug/mL) for 6 h. Luciferase activity is measured, and the IC₅0 is calculated.
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| Cell Assay |
For anti-inflammatory activity assessment, RAW 264.7 macrophages are seeded in 96-well plates (1×10⁴ cells/well) in DMEM with 10% FBS and incubated overnight. Cells are pre-treated with 21-Acetoxypregnenolone (0.1-100 uM) for 1 h, then stimulated with LPS (1 ug/mL) for 24 h. Culture supernatants are collected for measurement of TNF-alpha, IL-6, and NO (Griess reagent). iNOS and COX-2 protein levels are assessed by Western blotting in cell lysates. For NF-kappaB translocation, cells are fixed and stained with anti-p65 antibody and DAPI, and localization is visualized by confocal microscopy. Cell viability is assessed by MTT assay. The IC₅0 for inhibition of cytokine production is calculated from dose-response curves. Dexamethasone (0.1-10 uM) is used as a positive control.
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| Animal Protocol |
Carrageenan-induced paw edema model in rats: Male Sprague-Dawley rats (180-200 g, n=8-10/group) are fasted overnight. 21-Acetoxypregnenolone is formulated in 0.5% methylcellulose or 5% DMSO + 5% Tween 80 + 90% saline and administered orally at doses of 10, 25, 50, 100 mg/kg. One hour later, 0.1 mL of 1% carrageenan in saline is injected into the subplantar region of the right hind paw. Paw volume is measured by plethysmometer at 0, 1, 2, 3, 4, 6 h post-injection. The percentage inhibition of paw edema is calculated relative to vehicle control. Indomethacin (10 mg/kg) is used as a positive control. At the endpoint (6 h), animals are euthanized, and gastric mucosa is examined for ulcers or lesions. Adjuvant-induced arthritis (AIA) model: Male Lewis rats (150-200 g) are injected with heat-killed Mycobacterium tuberculosis (0.5-1 mg) in Freund‘s incomplete adjuvant (FIA) into the tail base. 21-Acetoxypregnenolone (10-50 mg/kg, oral) is administered daily for 21 days. Paw volume, clinical scores (0-4), and radiography are assessed.
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| ADME/Pharmacokinetics |
No specific PK data for 21-Acetoxypregnenolone is available. As a lipophilic steroid derivative (MW 374.51, LogP ~4-5), it is expected to have high oral absorption and good cell permeability. The compound likely crosses the blood-brain barrier due to its lipophilicity. It is probably metabolized in the liver by CYP450 enzymes (CYP3A4) via deacetylation (to pregnenolone), hydroxylation, and conjugation (glucuronidation, sulfation). The half-life in rodents is expected to be 2-6 hours. Excretion is primarily in urine and feces as metabolites. For research use, the compound is soluble in DMSO (50-100 mM), ethanol, and organic solvents, with poor water solubility. For in vivo studies, it can be formulated in 5% DMSO + 40% PEG300 + 5% Tween 80 + 50% saline or in corn oil.
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| Toxicity/Toxicokinetics |
For 21-Acetoxypregnenolone, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Standard safety precautions for handling steroidal compounds apply: use PPE (gloves, lab coat, safety goggles), work in a well-ventilated area (fume hood), avoid inhalation and skin contact. Storage: powder at -20degC for 3 years, 4degC for 2 years; in solvent (DMSO) at -80degC for 1 year, -20degC for 6 months. Protect from light.
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| References | |
| Additional Infomation |
21-Acetoxypregnenolone is a corticosteroid hormone.
See also: Dimethyltestosterone (related drugs). 21-Acetoxypregnenolone (CAS# 566-78-9) is a research-grade steroidal anti-inflammatory compound, a derivative of pregnenolone. It is not an FDA-approved drug. It has been investigated for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. It is used in research on inflammation, arthritis, and steroid hormone signaling. For research use only, not for diagnostic or therapeutic applications. |
| Molecular Formula |
C23H34O4
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|---|---|
| Molecular Weight |
374.52
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| Exact Mass |
374.246
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| CAS # |
566-78-9
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| PubChem CID |
248856
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
667
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| Defined Atom Stereocenter Count |
7
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| SMILES |
CC(=O)OCC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C
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| InChi Key |
MDJRZSNPHZEMJH-MTMZYOSNSA-N
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| InChi Code |
InChI=1S/C23H34O4/c1-14(24)27-13-21(26)20-7-6-18-17-5-4-15-12-16(25)8-10-22(15,2)19(17)9-11-23(18,20)3/h4,16-20,25H,5-13H2,1-3H3/t16-,17-,18-,19-,20+,22-,23-/m0/s1
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| Chemical Name |
[2-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[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 | 2.6701 mL | 13.3504 mL | 26.7008 mL | |
| 5 mM | 0.5340 mL | 2.6701 mL | 5.3402 mL | |
| 10 mM | 0.2670 mL | 1.3350 mL | 2.6701 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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