3,5-Diiodo-L-thyronine

• CAS: 1041-01-6
• Catalog Number: ACM1041016-2
• Category: Main Products
• Molecular Weight: 525.08
• Molecular Formula: C15H13I2NO4
• Synonyms: Diiodothyronine
• IUPAC Name: (2S)-2-Amino-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propanoic acid
• SMILES: C1=CC(=CC=C1O)OC2=C(C=C(C=C2I)CC(C(=O)O)N)I
• InChI: InChI=1S/C15H13I2NO4/c16-11-5-8(7-13(18)15(20)21)6-12(17)14(11)22-10-3-1-9(19)2-4-10/h1-6,13,19H,7,18H2,(H,20,21)/t13-/m0/s1
• InChI Key: ZHSOTLOTTDYIIK-ZDUSSCGKSA-N
• Boiling Point: 559.4±50.0 °C
• Melting Point: 255-260 °C
• Flash Point: 292.1 °C
• Density: 2.095±0.06 g/cm³
• Appearance: Solid
• Storage: Keep in dark place, sealed in dry, store in freezer, under -20 °C
• Complexity: 365
• EC Number: 213-867-7
• Exact Mass: 524.89340
• Hazard Statements: Xn
• Isomeric SMILES: C1=CC(=CC=C1O)OC2=C(C=C(C=C2I)C[C@@H](C(=O)O)N)I
• Monoisotopic Mass: 524.89340
• pKa: 2.15±0.30(Predicted)
• Refractive Index: 1.726
• Safety Description: 24/25
• Topological Polar Surface Area: 92.8 Ų
• WGK Germany: 3

Case Study

Physiological Effects of 3,5-Diiodo-L-Thyronine in Dietary Supplements

Hernandez A. Endocrinology, 2015, 156(1), 5-7.

3,5-Diiodo-L-thyronine (T2) is a thyroid hormone (TH) metabolite that has found its way into the formulations of many drugs. 3,5-Diiodo-L-thyronine was observed to have rapid induction of hepatic oxygen consumption and oxidative capacity and was therefore used as a metabolic inducer. Outlined below are some of the physiological effects that T2 may have as a dietary supplement ingredient.
Physiological Effects of 3,5-Diiodo-L-Thyronine
· T2 has positive effects on mitochondrial function, fat mass, lipid metabolism, and insulin resistance, supporting the use of T2 to enhance metabolism.
· Although T2's ability to increase metabolism is unquestionable, it is unclear which conditions allow its safe and effective use in humans.
· The researchers used an obese mouse model to analyze the physiological effects of T2. These effects include inhibition of the HPT axis, reductions in fat mass, serum leptin, and cholesterol, and increases in lean body mass, food intake, and hepatic expression of TH-dependent genes related to lipid metabolism.
· In addition, studies have shown that in addition to increasing metabolism and reducing fat mass, T2 administration can lead to HPT axis suppression, increased food intake, and cardiac hypertrophy.

Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals

Giammanco, M., Di Liegro, C. M., Schiera, G., & Di Liegro, I. International Journal of Molecular Sciences, 2020, 21, 4140.

3,5-diiodo-L-thyronine (3,5-T2) is an endogenous catabolite of thyroid hormones (THs) whose metabolism and mechanisms of action in mammals have been examined alongside those of T3 and T4. Although THs were early proposed as anti-obesity drugs for their ability to increase energy expenditure, their clinical use is limited by toxic effects, especially on the heart. 3,5-diiodo-L-thyronine attracts increasing interest because its metabolic effects resemble those of T3 but appear safer.
The mitochondria are the main target of 3,5-diiodo-L-thyronine. Acting on mitochondrial function and oxidative stress, 3,5-diiodo-L-thyronine prevents and reverts hepatic steatosis induced by a hyper-lipid diet, while reducing circulating low-density lipoproteins (LDL) and triglycerides. Unlike T3, whose canonical action is mediated by nuclear receptors regulating gene transcription, 3,5-diiodo-L-thyronine acts through non-genomic pathways that involve mitochondrial and cell-membrane binding sites, including direct interaction with cytochrome c oxidase.
Possible clinical applications of 3,5-diiodo-L-thyronine include lipid dysmetabolism, nonalcoholic fatty liver disease and obesity, where its mitochondrial mechanisms and reduced thyrotoxicity offer a pharmacological advantage over T3.

Direct and Rapid Effects of 3,5-Diiodo-L-Thyronine (T2) on Energy Metabolism

Moreno, M., Giacco, A., Di Munno, C., & Goglia, F. Molecular and Cellular Endocrinology, 2017, 458, 121-126.

3,5-diiodo-L-thyronine (T2) directly and rapidly affects energy metabolism at the cellular, rather than nuclear, level. In vivo, picomolar concentrations of 3,5-diiodo-L-thyronine stimulate oxygen consumption in perfused livers from hypothyroid rats within 1 h of injection (versus 20 h for T3), an action independent of de novo transcription and of deiodinase activity.
The key target of 3,5-diiodo-L-thyronine is the mitochondrion: it specifically binds the Va subunit of cytochrome c oxidase (COX), abolishes the allosteric ATP inhibition of the complex and produces a calorigenic effect. In rats fed a high-fat diet, administration of 3,5-diiodo-L-thyronine (25 µg/100 g body weight for 4 weeks) prevents body-weight gain, liver adiposity, hyperlipidemia and insulin resistance without thyrotoxicosis, and reduces pre-existing hepatic fat accumulation by increasing mitochondrial fatty acid oxidation coupled with uncoupling and by lowering oxidative stress. The mechanism involves rapid hepatic fatty acid oxidation via sirtuin 1 activation and partial restoration of respiratory complex I and II levels altered by the high-fat diet.
In vitro, 3,5-diiodo-L-thyronine reduces lipid droplets in fatty hepatocytes by recruiting triglyceride lipase (ATGL) to lipid droplet surfaces, up-regulates CPT1, and stimulates COX activity and mitochondrial uncoupling independently of nuclear thyroid receptors, supporting its anti-obesity and anti-steatotic potential.

Custom Reviews

July 21, 2024

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Highly Effective in Regulating Gene Activity
3,5-Diiodo-L-thyronine from Alfa Chemistry to be a highly effective product in regulating gene activity. The off-white solid compound is easy to work with and has provided promising results in my studies related to homeostasis, lipid metabolism, and insulin resistance. I have also found it to be useful in the early detection and treatment of congenital or drug-induced hypothyroidism. Overall, I highly recommend this product for anyone conducting research in the field of thyroid hormones and gene regulation.

Synthetic Use

Upstream Synthesis Route 1

• 178877-78-6

• 1041-01-6

Reference: [1] Synthetic Communications, 2013, vol. 43, # 10, p. 1439 - 1446

Upstream Synthesis Route 2

• 54337-43-8
• 300-39-0

• 1041-01-6

Reference: [1] Tetrahedron Letters, 1997, vol. 38, # 40, p. 6965 - 6968

Upstream Synthesis Route 3

• 623-05-2

• 1041-01-6

Reference: [1] Tetrahedron Letters, 1997, vol. 38, # 40, p. 6965 - 6968

Downstream Synthesis Route 1

• 1041-01-6

• 51-48-9

Reference: [1]Patent: WO2015/151013,2015,A1 .Location in patent: Page/Page column 14

Downstream Synthesis Route 2

• 1041-01-6

• 6893-02-3

Reference: [1]Biochemical Journal,1953,vol. 53,p. 645,647
[2]Biochemical Journal,1953,vol. 53,p. 645,647
[3]Biochemical Journal,1953,vol. 53,p. 645,647
[4]Organic Process Research and Development,2014,vol. 18,p. 1175 - 1180
[5]Patent: JP5833222,2015,B2

* For details of the synthesis route, please refer to the original source to ensure accuracy.