| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Thyroid Peroxidase (TPO). Methimazole D3 acts by inhibiting thyroid peroxidase (TPO), the enzyme responsible for the iodination of tyrosine residues on thyroglobulin and the coupling of iodotyrosines to form thyroxine (T4) and triiodothyronine (T3). It does not block the release of preformed hormones, so clinical effects are delayed by several weeks.
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|---|---|
| ln Vitro |
Methimazole inhibits TPO activity with an IC50 of approximately 0.3-0.5 microM in cell-free enzyme assays. It acts as a substrate for TPO, trapping oxidized iodide and preventing its incorporation into thyroglobulin. Methimazole also has immunomodulatory effects, including reducing serum levels of thyroid-stimulating immunoglobulins in Graves‘ disease patients.
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| ln Vivo |
In rats, methimazole (0.4 mg/kg) inhibits the absorption of radiolabeled iodide by the thyroid gland and reduces plasma levels of T3 and T4 within 24-48 hours. Chronic administration (10 mg/kg/day for 14-21 days) induces goiter formation due to elevated TSH secondary to low thyroid hormone levels, establishing a standard pharmacological model of hypothyroidism.
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| Enzyme Assay |
Cell-free TPO enzyme assays are performed using purified porcine or human TPO. The reaction mixture (200 microL) contains 50 mM phosphate buffer (pH 7.4), 0.5 mM KI, 0.5 mM H2O2, and varying concentrations of methimazole D3. After adding TPO (0.2 U/mL), the reaction is incubated at 37degC for 10-30 minutes. The iodination reaction is stopped by adding 1% BSA and 10% trichloroacetic acid. Precipitated protein is separated by centrifugation, and the iodine incorporation is measured by absorbance at 350 nm or by radioactivity when using ¹2⁵I.
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| Cell Assay |
Not applicable, as thyroid peroxidase is an enzyme expressed on the apical membrane of thyroid follicular cells, and methimazole acts directly on this enzyme rather than through a cell surface receptor. FRTL-5 rat thyroid cells are used for cellular assays: cells are cultured in Coon's modified Ham's F-12 medium supplemented with 5% calf serum and TSH. After 48-hour treatment, TPO activity and T3/T4 secretion are measured by ELISA.
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| Animal Protocol |
Male Sprague-Dawley rats (200-250 g) are used. Animals receive oral methimazole D3 (1-10 mg/kg) or vehicle once daily for 14 days. On day 15, blood is collected from the retro-orbital plexus or cardiac puncture. Serum T3, T4, and TSH levels are quantified by radioimmunoassay (RIA). Thyroid glands are excised, weighed, and fixed in formalin for histological assessment of follicular cell hypertrophy and colloid depletion.
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| ADME/Pharmacokinetics |
Methimazole D3 is intended as an internal standard for bioanalytical LC-MS/MS quantification. The parent drug methimazole is rapidly and completely absorbed from the GI tract (>90%), with an oral bioavailability of ~93%. It has a short plasma half-life of 5-6 hours but a long intrathyroidal half-life. It is minimally protein bound (~10%) and is primarily excreted in urine.
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| Toxicity/Toxicokinetics |
Methimazole is well-tolerated, but serious adverse reactions occur in 3-12% of patients. The most common side effects include rash, pruritus, nausea, and arthralgia. Agranulocytosis occurs in 0.2-0.5% of patients and is dose-dependent. Hepatotoxicity (cholestatic jaundice) and vasculitis are rare. Methimazole is contraindicated in pregnancy due to risk of aplasia cutis.
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| References | |
| Additional Infomation |
Methimazole was FDA-approved in 1949 for the treatment of hyperthyroidism, including Graves' disease, toxic adenoma, and multinodular goiter. It is preferred over propylthiouracil in non-pregnant adults due to better safety and once-daily dosing. The D3-labeled version is exclusively a research internal standard for precise drug quantification in biological samples from clinical studies.
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| Molecular Formula |
C4H3D3N2S
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|---|---|
| Molecular Weight |
117.187
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| Exact Mass |
114.025
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| CAS # |
1160932-07-9
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| Related CAS # |
Methimazole;60-56-0
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| PubChem CID |
42641318
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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 |
154.8±23.0 °C at 760 mmHg
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| Flash Point |
47.4±22.6 °C
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| Vapour Pressure |
3.1±0.3 mmHg at 25°C
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| Index of Refraction |
1.667
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| LogP |
-0.34
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
7
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| Complexity |
119
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])N1C=CNC1=S
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| InChi Key |
PMRYVIKBURPHAH-FIBGUPNXSA-N
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| InChi Code |
InChI=1S/C4H6N2S/c1-6-3-2-5-4(6)7/h2-3H,1H3,(H,5,7)/i1D3
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| Chemical Name |
3-(trideuteriomethyl)-1H-imidazole-2-thione
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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 | 8.5332 mL | 42.6658 mL | 85.3315 mL | |
| 5 mM | 1.7066 mL | 8.5332 mL | 17.0663 mL | |
| 10 mM | 0.8533 mL | 4.2666 mL | 8.5332 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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