| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Thyroid hormone receptors (THRs), specifically thyroid hormone receptor alpha (THRalpha) and beta (THRbeta), which are nuclear hormone receptors that regulate gene transcription. L-Thyroxine (T4) is a prohormone that is converted to the more active form triiodothyronine (T3) by deiodinase enzymes. T3 binds to THRs with high affinity, regulating metabolism, growth, and development. The 13C6-labeled analog preserves the identical biological recognition properties as native T4.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers that influence measurement during the drug development process. It's possible that the pharmacokinetics and functional range of medications contribute to the concern over mutagenesis [1].
In vitro, the unlabeled L-thyroxine (T4) demonstrates high-affinity binding to thyroid hormone receptors (THRalpha and THRbeta) after conversion to T3. It regulates the expression of genes involved in metabolism, cardiac function, and neural development. T4 is also a substrate for deiodinases (DIO1, DIO2, DIO3) that convert it to the active T3 or inactive reverse T3 (rT3). The 13C6-labeled version has identical receptor-binding properties but is used as an analytical standard. |
| ln Vivo |
In vivo, L-thyroxine (T4) is the primary hormone secreted by the thyroid gland and circulates bound to transport proteins (TBG, transthyretin, albumin). It is converted to T3 in peripheral tissues by type 1 and type 2 iodothyronine deiodinases, and T3 exerts metabolic effects by binding to nuclear thyroid hormone receptors. The 13C6-labeled version has identical biological properties but is used as an internal standard for quantification in pharmacokinetic studies.
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| Enzyme Assay |
A standard in vitro receptor binding assay for thyroid hormones is performed using purified thyroid hormone receptor (THRalpha or THRbeta) protein and a radiolabeled tracer such as 125I-T3. Varying concentrations of the unlabeled or labeled compound are incubated with the receptor and tracer. Bound ligand is separated from free ligand by filtration or charcoal adsorption, and radioactivity is counted to calculate the inhibition constant (Ki) or half-maximal inhibitory concentration (IC50). The 13C6-labeled version would compete identically.
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| Cell Assay |
A functional cellular assay for thyroid hormone activity uses a luciferase reporter gene assay. Cells (e.g., HEK293T) are co-transfected with a plasmid containing a thyroid hormone response element (TRE) driving firefly luciferase expression and a Renilla control plasmid. After transfection, cells are treated with varying concentrations of L-thyroxine (or the 13C6-labeled analog) for 24-48 hours. Luciferase activity is measured to determine the half-maximal effective concentration (EC50) for transcriptional activation.
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| Animal Protocol |
In vivo animal studies for thyroid hormones often use thyroidectomized rats that are rendered hypothyroid. Animals are administered L-thyroxine (or the labeled analog) at various doses via subcutaneous injection or oral gavage. Endpoints include measurement of serum TSH levels (which should decrease), metabolic rate (oxygen consumption), body temperature, heart rate, and organ weights (e.g., liver, kidney). Gene expression of thyroid hormone-responsive targets (e.g., Malx1, Spot14) in tissues is measured by qPCR.
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| ADME/Pharmacokinetics |
L-Thyroxine (T4) has a plasma half-life of approximately 6-7 days in humans and a volume of distribution of about 10-15 L. It is highly protein-bound (>99.9%) to thyroxine-binding globulin (TBG), transthyretin, and albumin. The 13C6-labeled version is expected to have identical pharmacokinetic properties. In research settings, T4 is administered orally or intravenously. Oral bioavailability is approximately 80%. T4 undergoes deiodination in the liver and kidneys to produce the active T3 and inactive rT3.
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| Toxicity/Toxicokinetics |
L-Thyroxine is generally well-tolerated at therapeutic doses but toxicity can occur with overdosage, causing symptoms of hyperthyroidism including tachycardia, weight loss, heat intolerance, anxiety, and cardiac arrhythmias. Chronic overdosage can lead to osteoporosis and atrial fibrillation. The 13C6-labeled version is not a therapeutic product but a research standard, and should be handled as a potent hormone with potential endocrine activity. Animal studies would require appropriate safety and ethical approvals.
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| References |
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-246.
[2]. Arici M, et al. Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients. Endocr J. 2018 Mar 28;65(3):317-323. [3]. Corriveau S, et al. Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animalmodel. J Clin Transl Endocrinol. 2015 Sep 9;2(4):144-149. |
| Additional Infomation |
L-Thyroxine-13C6-1 is a stable isotope-labeled internal standard for the accurate LC-MS/MS quantification of endogenous L-thyroxine in biological matrices. It is not intended for therapeutic use. Unlabeled L-thyroxine (levothyroxine) is a synthetic thyroid hormone widely prescribed for the treatment of hypothyroidism (underactive thyroid). It is one of the most commonly prescribed medications worldwide and is on the World Health Organization's List of Essential Medicines. The 13C6-labeled version is used as a certified reference material (CRM) in clinical mass spectrometry assays for thyroid function testing and pharmacokinetic studies.
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| Molecular Formula |
C15H11I4NO4
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|---|---|
| Molecular Weight |
782.825962305069
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| Exact Mass |
782.706
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| CAS # |
1217780-14-7
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| Related CAS # |
L-Thyroxine;51-48-9
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| PubChem CID |
46783077
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
420
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1=C(C=C(C(=C1I)O[13C]2=[13CH][13C](=[13C]([13C](=[13CH]2)I)O)I)I)C[C@@H](C(=O)O)N
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| InChi Key |
XUIIKFGFIJCVMT-DOEZJOBUSA-N
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| InChi Code |
InChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1/i4+1,5+1,7+1,8+1,9+1,13+1
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| Chemical Name |
(2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodo(1,2,3,4,5,6-13C6)cyclohexa-1,3,5-trien-1-yl)oxy-3,5-diiodophenyl]propanoic acid
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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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2774 mL | 6.3871 mL | 12.7742 mL | |
| 5 mM | 0.2555 mL | 1.2774 mL | 2.5548 mL | |
| 10 mM | 0.1277 mL | 0.6387 mL | 1.2774 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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