Endogenous Metabolite
Dextrothyroxine binds to thyroid hormone receptors, particularly THRA (thyroid hormone receptor alpha). It acts as a thyroid hormone analog and can influence gene expression. Dextrothyroxine inhibits the conversion of T4 to T3 by inhibiting 5'-deiodinase. It influences cell function by affecting cell signaling pathways and gene expression.

Triiodothyronine (T3), thyroxine (T4), basal TSH and TSH after stimulation with TRH were determined in healthy subjects and patients treated with D-thyroxine (DT4). After a dosage of 6 mg DT4 the D/L T4 plasma concentration rose about 4-fold 4 hours after application and was only moderately elevated 14 hours later. To achieve constantly elevated T4 levels 3 mg DT4 were applied in the further experiment every 12 hours. The D/L T4 plasma concentration rose 2.5-4-fold and there was a small but significant increase of the D/L T3 plasma concentration. 74 hours after onset of treatment basal TSH was below detectable limits and the increase of TSH 30 min after injection of 200 mug TRH (TRH test) was only about 15% compared to zero time. The time course of TSH suppression was investigated after treatment with DT4 and LT4 (single dosage of 3 mg). TRH-tests were performed before, 10, 26, 50 and 74 hours after the first dosage of D or LT4. There was no difference in the time course of basal TSH and TSH stimulated by TRH. In 10 patients on DT4 long-term therapy, basal and stimulated TSH were found to be below the detectable limits of 0.4 mug/ml. Our results show that (1) plasma half-life of DT4 is less than 1 day, (2) TSH suppression after D and LT4 treatment is very similar, and (3) in patients on long-term DT4 treatment, TSH plasma concentration is below detectable limits even after stimulation with TRH [2].
In vitro, dextrothyroxine binds to thyroid hormone receptors and activates thyroid hormone-mediated transcription. It inhibits the conversion of T4 to T3. Its effects on gene expression and cell function have been characterized in various cell culture models.

In an attempt to compare the cholesterol-lowering effects of equivalent doses of D- and L-thyroxine, 10 euthyroid, hypercholesterolemic subjects were treated with graded doses of each medication in a cross-over design using thyrotropin suppression following thyrotropin-releasing hormone administration as the end-point. The mean thyrotropin-suppressive dose of D-thyroxine was 2.4 +/- 0.66 mg per day, which resulted in mean reductions of 10 percent in total plasma cholesterol, 10 percent in plasma low-density lipoprotein cholesterol, and 11 percent in plasma high-density lipoprotein cholesterol. The mean thyrotropin-suppressive dose of L-thyroxine was 135 +/- 46 micrograms per day, which resulted in mean reductions of 7 percent in total plasma cholesterol, 6 percent in plasma low-density lipoprotein cholesterol, and 14 percent in plasma high-density lipoprotein cholesterol. The reductions in total, low-density, and high-density cholesterol achieved with D-thyroxine were not significantly different from those achieved with L-thyroxine. Neither medication produced a significant increase in heart rate or ventricular ectopy as determined by Holter monitoring. These data do not support the belief that D-thyroxine has a preferential cholesterol-lowering effect in humans when compared with equivalent doses of L-thyroxine. In addition, both D- and L-thyroxine reduced plasma high-density lipoprotein cholesterol [1].
In vivo, dextrothyroxine acts in the liver to stimulate the formation of low-density lipoprotein (LDL) and, to a much greater extent, to increase the catabolism of LDL. This leads to increased excretion of cholesterol and bile acids via the biliary route. Dextrothyroxine has been used for the study of hypercholesterolemia.

In vitro receptor binding assays for dextrothyroxine typically measure its affinity for thyroid hormone receptors. Radiolabeled T3 is displaced by increasing concentrations of the compound to determine binding affinity. Functional assays measure the compound's ability to activate thyroid hormone-mediated transcription.

Cell-based assays for dextrothyroxine involve treating cells expressing thyroid hormone receptors with the compound and measuring receptor-mediated transcriptional activity. Cells transfected with a thyroid hormone-responsive reporter gene are treated with varying concentrations of the compound. Reporter gene activity is measured, and EC50 values are calculated.

In vivo animal studies for dextrothyroxine are conducted in models of hypercholesterolemia. The compound is administered, and its effects on cholesterol levels, LDL levels, and bile acid excretion are assessed.

Dextrothyroxine has a molecular weight of 776.87 and a molecular formula of C15H11I4NO4. It is soluble in DMSO. For storage, it should be kept at -20°C.

Dextrothyroxine can cause adverse effects related to thyroid hormone excess, including tachycardia, arrhythmias, and weight loss. It is contraindicated in patients with hyperthyroidism.

[1]. Comparison of effectiveness of thyrotropin-suppressive doses of D- and L-thyroxine in treatment of hypercholesterolemia. Am J Med. 1984 Sep;77(3):475-81.

[2]. Influence of D-thyroxine on plasma thyroid hormone levels and TSH secretion. Horm Metab Res. 1977 Jan;9(1):69-73.

Dextrothyronine is the D-enantiomer of thyroxine, a derivative of thyroxine and D-tyrosine, and also the enantiomer of levothyroxine. Thyroxine is the main hormone secreted by the thyroid gland. It is synthesized from iodinated tyrosine (monoiodotyrosine) and iodotyrosine-coupled (diiodotyrosine) in thyroglobulin. Thyroxine is released from thyroglobulin via proteolysis and secreted into the bloodstream. Peripherally, thyroxine is deiodinated to form triiodothyronine, which has a broad stimulatory effect on cellular metabolism. Dextrothyronine is the dextrorotatory isomer of thyroxine and is a thyroid hormone with lipid-lowering activity. Dextrothyronine stimulates the production of low-density lipoprotein (LDL) and increases LDL catabolism, leading to increased excretion of cholesterol and bile acids via the biliary tract. This ultimately results in decreased serum cholesterol and LDL levels. It is the dextrorotatory isomer of synthetic thyroxine. See also: Dextrothyronine sodium (note moved here). Drug Indications Used to lower high cholesterol levels in the blood. Mechanism of Action Dextrothyronine is a lipid-lowering drug. Its mechanism of action is not fully understood, but dextrothyronine apparently acts in the liver, stimulating the production of low-density lipoprotein (LDL) and significantly increasing LDL catabolism. This leads to the excretion of cholesterol and bile acids in the feces via the biliary tract, thereby lowering serum cholesterol and LDL cholesterol. Dextrothyronine has no significant effect on high-density lipoprotein cholesterol (HDL). It also binds to thyroid receptors and, as a prohormone, acts as a substrate for iodine peroxidase. Pharmacodynamics Dextrothyronine is the dextrorotatory isomer of synthetic thyroxine and is a lipid-lowering drug.
Dextrothyroxine (D-T4) is the dextrorotary enantiomer of thyroxine, a thyroid hormone analog with antihyperlipidemic activity. It is used in research to study thyroid hormone signaling and cholesterol metabolism. It is a valuable research tool for studying the mechanisms of thyroid hormone action and for developing new therapeutic agents for hypercholesterolemia.

C15H11I4NO4

776.87

776.686

C, 23.19; H, 1.43; I, 65.34; N, 1.80; O, 8.24

51-49-0

D-Thyroxine sodium;137-53-1

8730

Light yellow to light brown solid

2.6±0.1 g/cm3

576.3±50.0 °C at 760 mmHg

225ºC

302.3±30.1 °C

0.0±1.7 mmHg at 25°C

1.795

Endogenous Metabolite

5.93

3

5

5

24

420

1

IC1C(=C(C([H])=C(C=1[H])C([H])([H])[C@]([H])(C(=O)O[H])N([H])[H])I)OC1C([H])=C(C(=C(C=1[H])I)O[H])I

XUIIKFGFIJCVMT-GFCCVEGCSA-N

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-/m1/s1

(2R)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid

Dethyrona; Debetrol; Dextrothyroxine; 51-49-0; (R)-2-Amino-3-(4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)propanoic acid; Choloxin; (2R)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid; DEXTROTHYROXINE SODIUM; D-T4; Biotirmone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~160.90 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (2.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (2.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)