| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
Flumethasone 21-acetate acts as a selective and potent agonist of the glucocorticoid receptor (GR). Upon binding to cytosolic GR, the complex translocates to the nucleus where it modulates gene transcription by binding to glucocorticoid response elements (GREs). It activates GR to inhibit nuclear factor kappa B (NF-kappaB)-mediated pro-inflammatory cytokine production (TNF-alpha, IL-1beta) and promotes anti-inflammatory gene expression (IL-10). It also exhibits mineralocorticoid receptor (MR) activity with EC50 of 0.494 nM in CV-1 cells expressing human receptors.
|
|---|---|
| ln Vitro |
In vitro, Flumethasone 21-acetate (0-200 nM; 0-24 h) reduces Nrf2 protein levels through GR-dependent proteasomal degradation in A549 and H460 lung cancer cells. At 100 nM for 4 hours, it enhances ubiquitination of Nrf2, an effect blocked by GR knockdown. The compound activates GR in CV-1 cells expressing human GR with an EC50 of 0.26 nM, demonstrating single-digit sub-nanomolar potency. It also induces tyrosine aminotransferase activity in hepatoma cells, regulating metabolic enzyme expression.
|
| ln Vivo |
In vivo, Flumethasone 21-acetate (10-⁸ to 10-⁶ moles/kg, intraperitoneal, single dose) induces a 4- to 10-fold increase in liver tyrosine aminotransferase activity, reflecting GR activation and metabolic regulation. As an anti-inflammatory corticosteroid, it suppresses edema, erythema, and immune responses in animal models of inflammation. The compound is orally active and exhibits sustained effects on cellular function including prolonged suppression of inflammatory responses and modulation of gene expression through GR-dependent pathways.
|
| Enzyme Assay |
Cell-free receptor binding protocol: CV-1 cells expressing human glucocorticoid receptors are lysed, and membranes are prepared. Flumethasone 21-acetate at various concentrations is incubated with [3H]-dexamethasone as a radioligand in binding buffer for 2-4 hours at room temperature. Bound and free radioligand are separated by filtration through glass fiber filters, and radioactivity is counted by scintillation to calculate binding affinity (EC50) and competition curves.
|
| Cell Assay |
Cell-based assay protocol: A549 or H460 cells are seeded in 6-well plates and treated with Flumethasone 21-acetate (50-200 nM) for 0-24 hours. For Western blot analysis, cells are lysed in RIPA buffer, and Nrf2 protein levels are quantified. For immunofluorescence, cells are fixed, permeabilized, stained with anti-Nrf2 antibody, and visualized by confocal microscopy. GR knockdown is achieved by siRNA transfection to confirm receptor-dependent effects.
|
| Animal Protocol |
Animal inflammation model protocol: Male rats or mice are treated with Flumethasone 21-acetate via intraperitoneal injection (10-⁸ to 10-⁶ moles/kg). For tyrosine aminotransferase induction, livers are harvested 4-6 hours post-treatment, homogenized, and enzyme activity is measured spectrophotometrically. For anti-inflammatory assessment, carrageenan-induced paw edema or croton oil-induced ear edema models are used, with compound administered orally or topically 1 hour before inflammatory challenge.
|
| ADME/Pharmacokinetics |
Flumethasone 21-acetate is orally active with good bioavailability. Following intraperitoneal administration, it achieves systemic distribution and induces hepatic tyrosine aminotransferase activity within 4-6 hours. The acetate ester likely undergoes hydrolysis to release active flumethasone. As a potent GR agonist with EC50 of 0.26 nM, it exhibits prolonged duration of action due to receptor-mediated transcriptional effects. The compound shows high plasma protein binding typical of corticosteroids, contributing to sustained half-life.
|
| Toxicity/Toxicokinetics |
Flumethasone 21-acetate exhibits dose-dependent toxicity characteristic of glucocorticoids, including immunosuppression, adrenal suppression, metabolic disturbances (hyperglycemia, lipolysis), and catabolic effects on bone and muscle with chronic exposure. At pharmacological doses, it is generally well-tolerated in short-term studies. However, long-term use or high doses may lead to Cushing's syndrome features, growth retardation in juveniles, delayed wound healing, and increased infection susceptibility.
|
| References |
[1]. Biagi GL, et al. Rm values of steroids as an expression of their lipophilic character in structure-activity studies. J Med Chem. 1975 Sep;18(9):873-83.
|
| Additional Infomation |
Flumethasone 21-acetate is a research compound not currently approved as a drug product. The parent compound flumethasone and its pivalate ester are used clinically in topical formulations for dermatological conditions such as eczema, psoriasis, and inflammatory skin disorders. Flumethasone 21-acetate serves as an analytical standard and research tool for studying glucocorticoid receptor pharmacology, anti-inflammatory mechanisms, and corticosteroid structure-activity relationships. Its high potency (120× relative to cortisol) makes it valuable for investigating GR-mediated gene regulation.
|
| Molecular Weight |
452.49
|
|---|---|
| Exact Mass |
452.201
|
| CAS # |
2823-42-9
|
| PubChem CID |
11155198
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.33g/cm3
|
| Boiling Point |
571.5ºC at 760mmHg
|
| Flash Point |
299.4ºC
|
| Vapour Pressure |
1.93E-15mmHg at 25°C
|
| Index of Refraction |
1.56
|
| LogP |
2.414
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
32
|
| Complexity |
945
|
| Defined Atom Stereocenter Count |
9
|
| SMILES |
CC(OCC([C@]1([C@H](C)C[C@H]2[C@@H]3C[C@H](F)C4=CC(C=C[C@]4(C)[C@@]3(F)[C@H](C[C@]12C)O)=O)O)=O)=O
|
| InChi Key |
ISSQQUKLQJHHOR-OSNGSNEUSA-N
|
| InChi Code |
InChI=1S/C24H30F2O6/c1-12-7-15-16-9-18(25)17-8-14(28)5-6-21(17,3)23(16,26)19(29)10-22(15,4)24(12,31)20(30)11-32-13(2)27/h5-6,8,12,15-16,18-19,29,31H,7,9-11H2,1-4H3/t12-,15+,16+,18+,19+,21+,22+,23+,24+/m1/s1
|
| Chemical Name |
[2-[(6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] acetate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 2.2100 mL | 11.0500 mL | 22.0999 mL | |
| 5 mM | 0.4420 mL | 2.2100 mL | 4.4200 mL | |
| 10 mM | 0.2210 mL | 1.1050 mL | 2.2100 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
