| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
CYP17A1 (17alpha-hydroxylase/C17,20-lyase)
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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].
This deuterated compound is chemically identical to the non-labeled compound, with deuterium atoms replacing four hydrogen atoms. It acts as a potent, selective, and irreversible inhibitor of CYP17A1, which is a key enzyme in androgen biosynthesis. Its biological activity is identical to the parent drug. |
| ln Vivo |
As an internal standard, abiraterone acetate-d4 is not studied for its own in vivo activity. However, the parent drug, abiraterone acetate, is a prodrug that is converted to abiraterone in vivo. Abiraterone potently inhibits CYP17A1, reducing the synthesis of androgens such as testosterone, which drives the growth of prostate cancer cells.
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| Enzyme Assay |
In a non-cellular enzyme assay, human CYP17A1 microsomes are incubated with the substrate 17alpha-hydroxyprogesterone and a NADPH-regenerating system. Increasing concentrations of the abiraterone internal standard are added to the mixture. The reaction is allowed to proceed for a defined time, then terminated by adding a stop solution. The product, androstenedione, is extracted and quantified by LC-MS. The IC50 value is determined from the dose-response curve.
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| Cell Assay |
For in vitro cell assays, cell lines like LNCaP (androgen-sensitive human prostate adenocarcinoma cells) are seeded in culture plates. The cells are treated with varying concentrations of abiraterone acetate (the unlabeled parent drug) for 3-5 days. The internal standard, abiraterone acetate-d4, is added to cell lysates prior to LC-MS analysis. Cell viability is assessed using an MTT assay to determine the compound's anti-proliferative effects.
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| Animal Protocol |
Abiraterone acetate-d4 is often used in animal PK studies as a tracer or internal standard. In a typical study, a known dose of unlabeled abiraterone acetate is administered to mice or rats. Blood samples are collected at time points (e.g., 0, 0.5, 1, 2, 4, 6, 8, 12, 24 h). A known amount of the deuterated internal standard is added to each sample. The plasma is processed for LC-MS analysis to quantify the concentration of the parent drug and its metabolite.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies with abiraterone acetate in humans show that it is rapidly absorbed, with peak plasma concentrations achieved within 2 hours of oral administration. It is highly bound to plasma proteins (99.8%). The terminal elimination half-life is approximately 10-12 hours. The prodrug is rapidly hydrolyzed to the active metabolite, abiraterone, which is the major circulating species.
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| Toxicity/Toxicokinetics |
Abiraterone acetate is clinically used as an anti-cancer drug (Zytiga®). Its toxicities include elevated liver enzymes, hypertension, hypokalemia, and fluid retention, related to its mechanism of CYP17A1 inhibition and subsequent mineralocorticoid excess. The deuterated form is a research tool and is not intended for human use, but shares the same toxicity profile if used at pharmacological doses.
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| References |
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| Additional Infomation |
Stable isotope-labeled drugs are essential for both drug development and therapeutic drug monitoring. The parent drug, abiraterone acetate, is FDA-approved for treating castration-resistant prostate cancer. The acetate is a pro-drug that improves oral bioavailability. The labeled form is used as an internal standard to accurately measure abiraterone concentrations in patient samples.
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| Molecular Formula |
C26H29D4NO2
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|---|---|
| Molecular Weight |
395.57
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| Related CAS # |
Abiraterone acetate;154229-18-2
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5280 mL | 12.6400 mL | 25.2800 mL | |
| 5 mM | 0.5056 mL | 2.5280 mL | 5.0560 mL | |
| 10 mM | 0.2528 mL | 1.2640 mL | 2.5280 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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