| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Mifepristone targets three major nuclear receptors: the progesterone receptor (PR), the glucocorticoid receptor (GR), and the androgen receptor (AR). It acts as an antagonist of these receptors, blocking the binding of their natural ligands (progesterone, cortisol, and testosterone, respectively). The tritium or deuterium labels do not alter its binding affinity.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
As a labeled version of an active drug, the in vitro activity of mifepristone-d3 is identical to unlabeled mifepristone. Mifepristone inhibits progesterone receptor activity with a Ki of 0.1 nM and glucocorticoid receptor activity with a Ki of 2.6 nM. It is highly selective for these receptors over the mineralocorticoid receptor (MR), estrogen receptor alpha (ERalpha), and ER beta. |
| ln Vivo |
Not applicable. The in vivo activity of mifepristone-d3 is equivalent to that of unlabeled mifepristone. In cell-based assays, mifepristone inhibits alkaline phosphatase activity stimulated by the progesterone receptor agonist R5020 and reporter transcription stimulated by dexamethasone or R5020 with IC₅0 values of 7, 5.9, and 1.3 nM, respectively. In a typical in vivo study, mifepristone (10 uM) inhibits the growth of 4-OHT-resistant MCF-7 breast cancer cells in vitro, and in an SKOV3 ovarian cancer nude mouse xenograft model, it inhibits tumor growth when administered at doses of 0.5 or 1 mg per day.
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| Enzyme Assay |
Standard receptor binding protocols are used to assess binding affinity (Ki). For the progesterone receptor (PR), the assay involves incubating a cytosolic preparation from a PR-rich source (e.g., rabbit uterus) with a high-affinity radioligand such as [3H]-R5020 (a synthetic progestin) and increasing concentrations of unlabeled mifepristone (or other PR ligands). Non-specific binding is determined using an excess of unlabeled R5020. Bound and free radioligand are separated by a rapid filtration method or charcoal adsorption, and the bound radioactivity is counted.
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| Cell Assay |
A standard cell-based assay for assessing the antagonist activity of mifepristone involves using a reporter cell line, such as T47D cells stably transfected with a MMTV-luciferase (mouse mammary tumor virus) reporter construct. The cells are treated with a fixed concentration of an agonist (e.g., 0.1 nM R5020 for PR, or 1 nM dexamethasone for GR) to induce high luciferase expression. Mifepristone is added in a dose titration series. After overnight incubation, the cells are lysed, and luciferase activity is measured. A dose-dependent decrease in luciferase activity demonstrates antagonism.
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| Animal Protocol |
For in vivo pharmacokinetic (PK) studies, mifepristone-d3 is spiked into biological samples (e.g., plasma, tissue homogenates) as an internal standard prior to sample processing. To prepare a sample, 20 microL of the internal standard solution containing mifepristone-d3 is added. The sample is then extracted with organic solvent to remove proteins. After centrifugation, the supernatant is injected onto an LC-MS/MS system, where the mass spectrometer specifically detects the parent drug and the deuterated internal standard.
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| ADME/Pharmacokinetics |
The deuterated version has nearly identical PK properties to the parent drug. Its pharmacokinetics are characterized by high protein binding (>98%) and extensive hepatic metabolism, primarily by the CYP3A4 isoenzyme. After oral administration, it has a terminal elimination half-life of approximately 18-48 hours.
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| Toxicity/Toxicokinetics |
Mifepristone-d3 itself is not used in toxicological studies. The parent compound, mifepristone, is well-tolerated at therapeutic doses used for medical abortion. Common side effects include abdominal cramping, nausea, and vomiting. At higher doses, it can cause headache, fatigue, and in rare cases, adrenal insufficiency due to its anti-glucocorticoid activity. Long-term use is associated with endometrial hyperplasia.
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| References |
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| Additional Infomation |
Mifepristone-d3 is a stable isotopically labeled internal standard, not a therapeutic agent for patients. It is an essential analytical tool for LC-MS/MS quantification of mifepristone in pharmacokinetic studies, bioequivalence studies, and clinical toxicology. Its non-deuterated form, mifepristone, is a prescription drug approved by the FDA for the medical termination of intrauterine pregnancy. The parent drug is also being investigated in clinical trials for other indications, including certain cancers and psychiatric disorders.
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| Molecular Formula |
C29H32D3NO2
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|---|---|
| Related CAS # |
Mifepristone;84371-65-3;Mifepristone-13C,d3
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| Appearance |
Typically exists as solid at room temperature
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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.) |
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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