| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma). Pioglitazone D4 is a potent and highly selective agonist of the nuclear receptor PPARgamma, which is predominantly expressed in adipose tissue, skeletal muscle, and liver. Activation of PPARgamma alters the transcription of genes involved in glucose and lipid metabolism, promoting adipocyte differentiation, increasing fatty acid uptake and storage, and reducing insulin resistance. The D4-labeled version acts as an analytical tracer and does not contribute to pharmacological activity.
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| ln Vitro |
Pioglitazone D4 is not tested for pharmacological activity as it is a stable isotope internal standard. The parent drug Pioglitazone is a PPARgamma agonist with an EC50 of 0.2-1.0 microM in cell-based transactivation assays. It increases insulin-stimulated glucose uptake in 3T3-L1 adipocytes with an EC50 of approximately 0.8 microM. Pioglitazone also inhibits the proliferation of various cancer cell lines at high micromolar concentrations (IC50 10-50 microM) and reduces IL-6 and TNFalpha production in LPS-stimulated macrophages.
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| ln Vivo |
In vivo, Pioglitazone (3-30 mg/kg orally) reduces plasma glucose, insulin, and triglyceride levels in insulin-resistant animal models, including db/db mice and Zucker fatty rats. It improves insulin sensitivity, lowers hyperglycemia, and delays the onset of diabetes. Pioglitazone D4, when used in a validated LC-MS/MS method, demonstrates a mean extraction recovery of pioglitazone from spiked human plasma of 94.92% across a validated range of 6.04 to 1503.21 ng/mL, confirming its utility as an internal standard.
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| Enzyme Assay |
PPARgamma binding assays are performed using a fluorescence polarization competitive binding assay format. Recombinant human PPARgamma ligand-binding domain (LBD, 10-20 nM) is incubated with a fluorescently labeled PPARgamma ligand (e.g., Fluormone™, 5 nM) and varying concentrations of unlabeled pioglitazone (or the unlabeled parent) in assay buffer (20 mM HEPES pH 7.4, 50 mM NaCl, 5 mM CHAPS, 1 mM DTT) for 2-4 hours at 4degC in the dark. Polarization is measured (excitation 485 nm, emission 520 nm). The IC50 is calculated, and the Ki is determined using the Cheng-Prusoff equation.
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| Cell Assay |
3T3-L1 preadipocytes are differentiated into mature adipocytes using insulin, dexamethasone, and isobutylmethylxanthine (IBMX) for 7 days. Differentiated adipocytes are starved in serum-free medium for 4 hours, then treated with varying concentrations of pioglitazone D4 (or unlabeled parent) (0.01-100 microM) for 24-48 hours. 2-Deoxy-[3H]glucose (0.5 microCi/mL) is added for 10-30 minutes to measure glucose uptake. Cells are washed, lysed, and radioactivity is counted. The EC50 for stimulation of glucose uptake is calculated. For analytical recovery, human plasma is spiked with known concentrations of pioglitazone and processed with Pioglitazone D4 as IS for LC-MS/MS.
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| Animal Protocol |
Female C57BL/6 db/db mice (6-8 weeks old, 30-40 g) are used as a model of type 2 diabetes. Mice are randomized (n=8-10 per group) based on baseline blood glucose levels. Pioglitazone D4 (internal standard) is not administered in efficacy studies; the unlabeled parent pioglitazone (3-30 mg/kg) or vehicle is administered orally once daily for 14-28 days. Blood glucose levels are measured weekly using a glucometer (tail vein). An oral glucose tolerance test (OGTT) is performed at study endpoint (2 g/kg glucose orally). Blood is collected by cardiac puncture for measurement of plasma insulin, triglycerides, and free fatty acids (FFAs) by ELISA/enzymatic assays. Liver and adipose tissues are harvested for histology (H&E).
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| ADME/Pharmacokinetics |
Pioglitazone D4 is a stable isotope-labeled internal standard (SIL-IS) with a mass shift of +4 Da. It has nearly identical chemical and chromatographic properties to unlabeled pioglitazone, ensuring accurate normalization for analyte loss during sample preparation. Pioglitazone has an oral bioavailability of >80%, is >99% protein bound (primarily to albumin), and has a terminal half-life of 3-7 hours in humans (active metabolite half-life 16-24 hours). It is extensively metabolized by CYP2C8 (major) and CYP3A4 (minor).
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| Toxicity/Toxicokinetics |
Pioglitazone D4 is for research use only and not for human consumption. Pioglitazone (parent drug) carries a boxed warning for congestive heart failure (CHF) and is contraindicated in patients with symptomatic heart failure. Common adverse effects include weight gain (due to fluid retention and increased adiposity), peripheral edema, musculoskeletal pain, and headache. Rare but serious side effects include bladder cancer, hepatotoxicity, and bone fractures.
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| References | |
| Additional Infomation |
Pioglitazone (Actos) was FDA-approved in 1999 for the treatment of type 2 diabetes mellitus (T2DM) as monotherapy or in combination with metformin, sulfonylureas, or insulin. Pioglitazone D4 is a research internal standard for LC-MS/MS bioanalysis, used in pharmacokinetic (PK) studies, bioequivalence trials, therapeutic drug monitoring (TDM), and drug-drug interaction studies involving CYP2C8 and CYP3A4 inhibitors. It is essential for the precise quantification of pioglitazone in biological matrices.
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| Molecular Formula |
C19H16D4N2O3S
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|---|---|
| Molecular Weight |
360.463
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| Exact Mass |
360.145
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| CAS # |
1134163-29-3
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| Related CAS # |
Pioglitazone;111025-46-8
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| PubChem CID |
25235523
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
575.4±45.0 °C at 760 mmHg
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| Flash Point |
301.8±28.7 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.611
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| LogP |
2.94
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
25
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| Complexity |
466
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C1=C(C(=C(C(=C1CC2C(=O)NC(=O)S2)[2H])[2H])OCCC3=NC=C(C=C3)CC)[2H]
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| InChi Key |
HYAFETHFCAUJAY-YBNXMSKUSA-N
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| InChi Code |
InChI=1S/C19H20N2O3S/c1-2-13-3-6-15(20-12-13)9-10-24-16-7-4-14(5-8-16)11-17-18(22)21-19(23)25-17/h3-8,12,17H,2,9-11H2,1H3,(H,21,22,23)/i4D,5D,7D,8D
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| Chemical Name |
5-[[2,3,5,6-tetradeuterio-4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
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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 | 2.7742 mL | 13.8712 mL | 27.7423 mL | |
| 5 mM | 0.5548 mL | 2.7742 mL | 5.5485 mL | |
| 10 mM | 0.2774 mL | 1.3871 mL | 2.7742 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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