Endogenous Metabolite; synthetic form of the thyroid hormone thyroxine (T4)

Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animal model[2]
Screening of thyroid function confirmed a hypothyroid state for all rats under iodine-free diet to which T4 was subsequently administered to counterbalance hypothyroidism. Results demonstrate that hypothyroidism significantly decreased contractile duration (-17%) and increased contractile frequency (+26%), while high doses of T4 increased duration (+200%) and decreased frequency (-51%). These results thus mimic the pattern of abnormal contractions previously observed in uterine tissue from T4-treated hypothyroid pregnant women. Conclusion: Our data suggest that changes in myometrial reactivity are induced by T4 treatment. Thus, in conjunction with our previous observations on human myometrial strips, management of hypothyroidism should be improved to reduce the rate of C-sections in this group of patients[2].

Adrenaline (cortogen) is converted to active adrenal cortex by the enzyme deiodinase (DIO), and the levels of TSH, the catalytic adrenaline, are correlated with this response. The adrenal cortex gets activated by DIO1 and DIO2, and gets deactivated by DIO3. In the negative feedback regulation of pituitary TSH, the actions of DIO1 and DIO2 are decisive [1]. The modulation of ion channels, pumps, and regulatory contractions is well-established for thyroxine (T3) and L-thyroxine (T4). Furthermore, it has been demonstrated that androgens influence charging excitation, calcium replenishment, contractile mortality, and the regulation of drug control and feeding by L-thyroxine and triiodothyronine. Significantly reduced levels of triiodothyronine and L-thyroxine were detected in the cohort fed an iodine-free diet for 12 weeks, as compared to the control group fed a regular diet (p<0.001). A rise in L-thyroxine levels (p=0.02) was noted in the group receiving low-dose L-thyroxine treatment, although triiodothyronine levels (p=0.19) remained nearly uniform with headache severity. Increases in circulation concentrations of triiodothyronine and L-thyroxine were observed after treatment with high-dose L-thyroxine as compared to the hypothyroid group that did not receive treatment (p<0.001 and p=0.004, each). Comparing the levels of thyroid hormone to the control values, there was a significant rise (p=0.03).

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Thyroid hormones play a vital role in the human body for growth and differentiation, regulation of energy metabolism, and physiological function. Hypothyroidism is a common endocrine disorder, which generally results from diminished normal circulating concentrations of serum thyroxine (fT4) and triiodothyronine (fT3). The primary choice in hypothyroidism treatment is oral administration of levothyroxine (L-T4), a synthetic T4 hormone, as approximately 100-125 μg/day. Generally, dose adjustment is made by trial and error approach. However, there are several factors which might influence bioavailability of L-T4 treatment. Genetic background could be an important factor in hypothyroid patients as well as age, gender, concurrent medications and patient compliance. The concentration of thyroid hormones in tissue is regulated by both deiodinases enzyme and thyroid hormone transporters. In the present study, it was aimed to evaluate the effects of genetic differences in the proteins and enzymes (DIO1, DIO2, TSHR, THR and UGT) which are efficient in thyroid hormone metabolism and bioavailability of L-T4 in Turkish population. According to our findings, rs225014 and rs225015 variants in DIO2, which catalyses the conversion of thyroxine (pro-hormone) to the active thyroid hormone, were associated with TSH levels. It should be given lower dose to the patients with rs225014 TT and rs225015 GG genotypes in order to provide proper treatment with higher effectivity and lower toxicity.[1]

Biochemical techniques[2]
ELISA assays were performed using a standard rat Thyroxine (T4) and T3 ELISA kit according to the manufacturer's protocol. Western blot analysis was performed exactly as previously described.

Female non-pregnant Sprague-Dawley rats (N = 22) were used and divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low T4 doses (20 μg/kg/day) and 4) with high T4 doses (100 μg/kg/day). Hypothyroidism was induced by an iodine-deficient diet. Isometric tension measurements were performed in vitro on myometrium tissues in isolated organ baths. Contractile activity parameters were quantified (amplitude, duration, frequency and area under the curve) using pharmacological tools to assess their effect.[2]

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Sprague–Dawley female rats (N = 22) were used. Non-pregnant rats were divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low doses of Levothyroxine (T4) (20 μg/kg/day) and 4) with high doses of T4 (100 μg/kg/day). Control rats (group 1) were fed with standard diet (TD.120461, Harlan laboratories, Madison, WI) while the intervention rats were fed with iodine-free diet for 12 weeks to induce hypothyroidism (groups 2–4) which was continued for four more weeks to allow screening of hypothyroid status and T4-treatment. Food and water (iodine-free diet) were available ad libitum. The hypothyroid group treated with low (group 3) or high doses of T4 (group 4) were injected intraperitoneally every 24 h with respectively 20 μg/kg/day and 100 μg/kg/day as previously described by Medeiros. Blood samples were collected for thyroid function screening at week 12 and 16 following the initiation of either the control or iodine-free diet. Hysterectomy was performed under general anesthesia (isoflurane 2%) at the end of the treatment and the two uterine horns were placed in physiological Krebs' solution until isometric tension measurements within no more than 1 h.[2]

Absorption, Distribution and Excretion
Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80% with the majority of the levothyroxine dose absorbed from the jejunum and upper ileum. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans, milk, and dietary fiber. Absorption may also decrease with age. In addition, many drugs affect T4 absorption including bile acide sequestrants, sucralfate, proton pump inhibitors, and minerals such as calcium (including in yogurt and milk products), magnesium, iron, and aluminum supplements. To prevent the formation of insoluble chelates, levothyroxine should generally be taken on an empty stomach at least 2 hours before a meal and separated by at least 4 hours from any interacting agents.
Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T₄ is eliminated in the stool. Urinary excretion of T₄ decreases with age.
Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins. Thyroid hormones do not readily cross the placental barrier.
Levothyroxine Sodium for Injection is administered via the intravenous route. Following administration, the synthetic levothyroxine cannot be distinguished from the natural hormone that is secreted endogenously.
Absorption of orally administered T4 from the gastrointestinal (GI) tract ranges from 40% to 80%. The majority of the levothyroxine dose is absorbed from the jejunum and upper ileum. The relative bioavailability of Synthroid tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 93%. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybean infant formula. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption.
Levothyroxine is variably absorbed from the GI tract (range: 40-80%). In animals, levothyroxine is absorbed in the proximal and middle jejunum; the drug is not absorbed from the stomach or distal colon and little, if any, absorption occurs in the duodenum. Studies in humans indicate that levothyroxine is absorbed from the jejunum and ileum and some absorption also occurs in the duodenum. The degree of absorption of levothyroxine from the GI tract depends on the product formulation and type of intestinal contents, including plasma protein and soluble dietary factors that may bind thyroid hormone and make it unavailable for diffusion. In addition, concurrent oral administration of infant soybean formula, soybean flour, cotton seed meal, walnuts, foods containing large amounts of fiber, ferrous sulfate, antacids, sucralfate, calcium carbonate, cation-exchange resins (e.g., sodium polystyrene sulfonate), simethicone, or bile acid sequestrants may decrease absorption of levothyroxine. The extent of levothyroxine absorption is increased in the fasting state and decreased in malabsorption states (e.g., sprue); absorption also may decrease with age.
For more Absorption, Distribution and Excretion (Complete) data for LEVOTHYROXINE (7 total), please visit the HSDB record page.

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Metabolism / Metabolites
Approximately 70% of secreted T₄ is deiodinated to equal amounts of T₃ and reverse triiodothyronine (rT₃), which is calorigenically inactive. T₄ is slowly eliminated through its major metabolic pathway to T₃ via sequential deiodination, where approximately 80% of circulating T₃ is derived from peripheral T₄. The liver is the major site of degradation for both T₄ and T₃, with T₄ deiodination also occurring at a number of additional sites, including the kidney and other tissues. Elimination of T₄ and T₃ involves hepatic conjugation to glucuronic and sulfuric acids. The hormones undergo enterohepatic circulation as conjugates are hydrolyzed in the intestine and reabsorbed. Conjugated compounds that reach the colon are hydrolyzed and eliminated as free compounds in the feces. Other minor T₄ metabolites have been identified.
Yields l-tyrosine in rabbit, in rat /From table/
Yields 3,3',5-triiodo-L-thyronine in man, rat, dog, rabbit. /From table/
Yields l-thyroxine-4'-beta-d-glucuronide in dog, in man, in rat. Yields l-thyroxine-4'-sulfate in dog. /From table/
Yields 3,3',5,5'-tetraiodothyropyruvic acid in rat. Yields l-thyronine in rat. /From table/
Yields 3,3'-diiodo-l-thyronine in dog. Yields 3,3',5,5'-tetraiodothyroacetic acid in man, in rat. /From table/

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Biological Half-Life
T₄ half-life is 6 to 7 days. T₃ half-life is 1 to 2 days.
In dogs orally administered levothyroxine has relatively ... short elimination half life when compared to humans. ... The serum half life is approximately 12-16 hours.
The usual plasma half-lives of thyroxine and triiodothyronine are 6-7 days and approximately 1-2 days, respectively. The plasma half-lives of thyroxine and triiodothyronine are decreased in patients with hyperthyroidism and increased in those with hypothyroidism.

Toxicity Summary
IDENTIFICATION AND USE: Levothyroxine occurs as crystals or needles. As a drug, levothyroxine sodium is used as replacement or supplemental therapy in congenital or acquired hypothyroidism. It is also used in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. The injection form of levothyroxine sodium is indicated for the treatment of myxedema coma. Levothyroxine has also been used in veterinary medicine. HUMAN EXPOSURE AND TOXICITY: The signs and symptoms of levothyroxine overdosage are those of hyperthyroidism. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Studies indicate that careful attention is necessary when initiating the administration of levothyroxine sodium to very-low-birth-weight infants. Ingestion of levothyroxine in children typically follows a benign course, but overdose can result in significant complications, including seizures and arrhythmias, both of which should be monitored for. In one genotoxicity study, the ability of thyroxine to induce sister chromatid exchange and micronuclei was tested in cultured human lymphocytes. Thyroxine exhibited weak clastogenic effects only at high concentrations. ANIMAL STUDIES: A single acute overdose in small animals is less likely to cause severe thyrotoxicosis than chronic overdosage. Vomiting, diarrhea, transition from hyperactivity to lethargy, hypertension, tachycardia, tachypnea, dyspnea, and abnormal pupillary light reflexes may be noted in dogs and cats. In dogs, clinical signs may appear within 1-9 hours after ingestion. Four pregnant New Zealand white rabbits received intramuscular levothyroxine at 250 ug/kg on days 25 and 26 of gestation. Maternal and fetal plasma-free levothyroxine concentration was higher than in controls, with the highest concentration noted at 14 days of neonatal period. Treatment resulted in fetal hyperglycemia and depletion of fetal liver glycogen content. Animal studies have not been performed to evaluate levothyroxine carcinogenic potential, mutagenic potential or effects on fertility.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Levothyroxine (T4) is a normal component of human milk. Limited data on exogenous replacement doses of levothyroxine during breastfeeding indicate no adverse effects in infants. The American Thyroid Association recommends that subclinical and overt hypothyroidism should be treated with levothyroxine in lactating women seeking to breastfeed. Adequate levothyroxine treatment during lactation may normalize milk production in hypothyroid lactating mothers with low milk supply. Levothyroxine dosage requirement may be increased in the postpartum period compared to prepregnancy requirements in patients with Hashimoto's thyroiditis.
◉ Effects in Breastfed Infants
Effects of exogenous thyroid hormone administration to mothers on their infant have not been reported. One case of apparent mitigation of cretinism in hypothyroid infants by breastfeeding has been reported, but the amounts of thyroid hormones in milk are not optimal, and this result has been disputed. The thyroid hormone content of human milk from the mothers of very preterm infants appears not to be sufficient to affect the infants' thyroid status. The amounts of thyroid hormones in milk are apparently not sufficient to interfere with diagnosis of hypothyroidism.
In a telephone follow-up study, 5 nursing mothers reported taking levothyroxine (dosage unspecified). The mothers reported no adverse reactions in their infants.
One mother who had undergone a thyroidectomy was taking levothyroxine 100 mcg daily as well as calcium carbonate and calcitriol. Her breastfed infant was reportedly "thriving" at 3 months of age.
A woman with propionic acidemia took levothyroxine 50 mcg daily as well as biotin, carnitine, and various amino acids while exclusively breastfeeding her infant for 2 months and nonexclusively for 10 months. At that time, the infant had normal growth and development.
◉ Effects on Lactation and Breastmilk
Adequate thyroid hormone serum levels are required for normal lactation. Replacing deficient thyroid levels should improve milk production caused by hypothyroidism. Supraphysiologic doses would not be expected to further improve lactation.

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Protein Binding
Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA) and albumin (TBA). The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone where only unbound hormone is metabolically active.

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Interactions
Antacids (e.g., aluminum hydroxide, magnesium hydroxide, calcium carbonate), simethicone, and sucralfate bind thyroid agents in the GI tract and delay or prevent their absorption. Calcium carbonate may form an insoluble chelate with levothyroxine, resulting in decreased levothyroxine absorption and increased serum thyrotropin concentrations; in vitro studies indicate that levothyroxine binds to calcium carbonate at acidic pH levels. To minimize or prevent this interaction, some clinicians recommend that these agents be administered approximately 4 hours apart when the drugs must be used concurrently with thyroid agents.
Serum concentrations of digitalis glycosides may be decreased in patients with hyperthyroidism or in patients with hypothyroidism in whom a euthyroid state has been achieved. Thus, therapeutic effects of digitalis glycosides may be reduced in these patients.
Drugs that induce hepatic microsomal enzymes (e.g., carbamazepine, phenytoin, phenobarbital, rifampin) may accelerate metabolism of thyroid agents, resulting in increased thyroid agent dosage requirements. Phenytoin and carbamazepine also reduce serum protein binding of levothyroxine, and total- and free-T4 may be reduced by 20-40%, but most patients have normal serum concentrations of thyrotropin (thyroid-stimulating hormone, TSH) and are clinically euthyroid. /Thyroid agents/
Bile acid sequestrants (e.g., cholestyramine resin, colestipol) bind thyroid agents in the GI tract and substantially impair their absorption. In vitro studies indicate that the binding is not readily reversible. To minimize or prevent this interaction, these agents should be administered at least 4 hours apart when the drugs must be used concurrently.
For more Interactions (Complete) data for LEVOTHYROXINE (14 total), please visit the HSDB record page.

[1]. Arici M, et al. Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients. Endocr J. 2018 Mar 28;65(3):317-323.
[2]. 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

L-thyroxine is the L-enantiomer of thyroxine. It has a role as a thyroid hormone, an antithyroid drug, a human metabolite and a mouse metabolite. It is a thyroxine, an iodophenol, a 2-halophenol, a L-phenylalanine derivative and a non-proteinogenic L-alpha-amino acid. It is a conjugate acid of a L-thyroxine(1-). It is an enantiomer of a D-thyroxine. It is a tautomer of a L-thyroxine zwitterion.
Levothyroxine is a synthetically produced form of thyroxine, a major endogenous hormone secreted by the thyroid gland. Also known as L-thyroxine or the brand name product Synthroid, levothyroxine is used primarily to treat hypothyroidism, a condition where the thyroid gland is no longer able to produce sufficient quantities of the thyroid hormones T4 (tetraiodothyronine or thyroxine) and T3 (triiodothyronine or [DB00279]), resulting in diminished down-stream effects of these hormones. Without sufficient quantities of circulating thyroid hormones, symptoms of hypothyroidism begin to develop such as fatigue, increased heart rate, depression, dry skin and hair, muscle cramps, constipation, weight gain, memory impairment, and poor tolerance to cold temperatures. In response to Thyroid Stimulating Hormone (TSH) release by the pituitary gland, a normally functioning thyroid gland will produce and secrete T4, which is then converted through deiodination (by type I or type II 5′-deiodinases) into its active metabolite T3. While T4 is the major product secreted by the thyroid gland, T3 exerts the majority of the physiological effects of the thyroid hormones; T4 and T3 have a relative potency of ~1:4 (T4:T3). T4 and T3 act on nearly every cell of the body, but have a particularly strong effect on the cardiac system. As a result, many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status. Prior to the development of levothyroxine, [DB09100] or desiccated thyroid, used to be the mainstay of treatment for hypothyroidism. However, this is no longer recommended for the majority of patients due to several clinical concerns including limited controlled trials supporting its use. Desiccated thyroid products contain a ratio of T4 to T3 of 4.2:1, which is significantly lower than the 14:1 ratio of secretion by the human thyroid gland. This higher proportion of T3 in desiccated thyroid products can lead to supraphysiologic levels of T3 which may put patients at risk of thyrotoxicosis if thyroid extract therapy is not adjusted according to the serum TSH.
Thyroxine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
Levothyroxine is a l-Thyroxine.
Levothyroxine has been reported in Homo sapiens and Bos taurus with data available.
Levothyroxine is a synthetic levoisomer of thyroxine (T4), similar to the endogenous hormone produced by the thyroid gland. Thyroxine is de-iodinated to form triiodothyronine (T3) in the peripheral tissues. T3 enters the cell and binds to nuclear thyroid hormone receptors, and the hormone-receptor complex in turn triggers gene expression and produces proteins required in the regulation of cellular respiration, thermogenesis, cellular growth and differentiation, and metabolism of proteins, carbohydrates and lipids. T4 and T3 also possess cardiac stimulatory effect.
Levothyroxine Sodium is the sodium salt of levothyroxine, a synthetic levoisomer of thyroxine (T4) that is similar to the endogenous hormone produced by the thyroid gland. In peripheral tissues, levothyroxine is deiodinated by 5'-deiodinase to form triiodothyronine (T3). T3 enters the cell and binds to nuclear thyroid hormone receptors; the activated hormone-receptor complex in turn triggers gene expression and produces proteins required in the regulation of cellular respiration; thermogenesis; cellular growth and differentiation; and the metabolism of proteins, carbohydrates and lipids. T3 also exhibits cardiostimulatory effects.
Thyroxine is a hormone synthesized and secreted by the thyroid gland containing four iodine atoms and is converted to triiodothyronine (T3) in the body, influencing metabolism and organ function.
The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.
See also: Liotrix (is active moiety of); Levothyroxine; Liothyronine (component of); Levothyroxine; liothyronine; thyroid (component of) ... View More ...

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Drug Indication
Levothyroxine is indicated as replacement therapy in primary (thyroidal), secondary (pituitary) and tertiary (hypothalamic) congenital or acquired hypothyroidism. It is also indicated as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

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Mechanism of Action
Levothyroxine is a synthetically prepared levo-isomer of the thyroid hormone thyroxine (T₄, a tetra-iodinated tyrosine derivative) that acts as a replacement in deficiency syndromes such as hypothyroidism. T₄ is the major hormone secreted from the thyroid gland and is chemically identical to the naturally secreted T₄: it increases metabolic rate, decreases thyroid-stimulating hormone (TSH) production from the anterior lobe of the pituitary gland, and, in peripheral tissues, is converted to T₃. Thyroxine is released from its precursor protein thyroglobulin through proteolysis and secreted into the blood where is it then peripherally deiodinated to form triiodothyronine (T₃) which exerts a broad spectrum of stimulatory effects on cell metabolism. T₄ and T₃ have a relative potency of ~1:4. Thyroid hormone increases the metabolic rate of cells of all tissues in the body. In the fetus and newborn, thyroid hormone is important for the growth and development of all tissues including bones and the brain. In adults, thyroid hormone helps to maintain brain function, food metabolism, and body temperature, among other effects. The symptoms of thyroid deficiency relieved by levothyroxine include slow speech, lack of energy, weight gain, hair loss, dry thick skin and unusual sensitivity to cold. The thyroid hormones have been shown to exert both genomic and non-genomic effects. They exert their genomic effects by diffusing into the cell nucleus and binding to thyroid hormone receptors in DNA regions called thyroid hormone response elements (TREs) near genes. This complex of T₄, T₃, DNA, and other coregulatory proteins causes a conformational change and a resulting shift in transcriptional regulation of nearby genes, synthesis of messenger RNA, and cytoplasmic protein production. For example, in cardiac tissues T₃ has been shown to regulate the genes for α- and β-myosin heavy chains, production of the sarcoplasmic reticulum proteins calcium-activated ATPase (Ca2+-ATPase) and phospholamban, β-adrenergic receptors, guanine-nucleotide regulatory proteins, and adenylyl cyclase types V and VI as well as several plasma-membrane ion transporters, such as Na+/K+–ATPase, Na+/Ca2+ exchanger, and voltage-gated potassium channels, including Kv1.5, Kv4.2, and Kv4.3. As a result, many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status. The non-genomic actions of the thyroid hormones have been shown to occur through binding to a plasma membrane receptor integrin aVb3 at the Arg-Gly-Asp recognition site. From the cell-surface, T₄ binding to integrin results in down-stream effects including activation of mitogen-activated protein kinase (MAPK; ERK1/2) and causes subsequent effects on cellular/nuclear events including angiogenesis and tumor cell proliferation.

C15H11I4NO4

776.8700

776.686

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

51-48-9

Thyroxine sulfate;77074-49-8;L-Thyroxine sodium salt pentahydrate;6106-07-6;L-Thyroxine sodium;55-03-8;L-Thyroxine-13C6-1;1217780-14-7;Biotin-(L-Thyroxine);149734-00-9;Biotin-hexanamide-(L-Thyroxine);2278192-78-0;Thyroxine hydrochloride-13C6;1421769-38-1;L-Thyroxine-13C6;720710-30-5;L-Thyroxine-13C6,15N;1431868-11-9

5819

Crystals
Needles

2.6±0.1 g/cm3

576.3±50.0 °C at 760 mmHg

235 °C

302.3±30.1 °C

0.0±1.7 mmHg at 25°C

1.795

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-LBPRGKRZSA-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-/m0/s1

(S)-2-amino-3-(4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)propanoic acid

L-Thyroxin, L Thyroxin, T4, Levothyroxine sodium, Levothyroxine sodium pentahydrate, Thyroxine; L-thyroxine; 51-48-9; thyroxine; thyroxin; Levothyroxin; Tetraiodothyronine; 3,3',5,5'-Tetraiodo-L-thyronine;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~250 mg/mL (~321.80 mM)
1M NaOH : 5 mg/mL (~6.44 mM)
H2O : < 0.1 mg/mL

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% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 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.)