D-α-Tocopherol succinate targets oxidative stress and free radicals. As a vitamin E derivative, it acts as a potent antioxidant, protecting cell membranes from damage caused by free radicals. The compound's mechanism of action involves scavenging free radicals and preventing lipid peroxidation. D-α-Tocopherol succinate also induces granulocyte-colony stimulating factor, which protects mice from gamma-radiation. The compound's antioxidant and radioprotective activities make it a valuable tool for studying oxidative stress-related diseases and radiation injury.

D-alpha-tocopheryl succinate (1-20 μM; 24 hours) is lethal to Heterocyclic O Cells [1]. D-alpha-tocopherol succinate (10 μM; 48 hours) reduces caspase-3 activity and shields HEI-OC1 cells from ototoxicity caused by cisplatin [1]. To TC-1 tumor cells, D-alpha-tocopheryl succinate (0-50 μM; 18 hours) is cytotoxic [2].
In vitro, D-α-Tocopherol succinate functions as a potent antioxidant. It protects cells from oxidative damage by scavenging free radicals and preventing lipid peroxidation. The compound's antioxidant activity can be measured using various in vitro assays such as DPPH radical scavenging and lipid peroxidation inhibition assays. D-α-Tocopherol succinate also induces granulocyte-colony stimulating factor, which may contribute to its radioprotective effects. The compound's antioxidant properties make it a valuable tool for studying oxidative stress and its role in various diseases.

Mice with TC-1 tumors were given injections of D-alpha-tocopherol succinate (1-2 mg/kg) three times, two days apart, for a period of 10 to 14 days. This treatment demonstrated antitumor effects [2].
In vivo, D-α-Tocopherol succinate protects mice from gamma-radiation by induction of granulocyte-colony stimulating factor. The compound has radioprotective effects, making it useful for studying radiation injury and protection. D-α-Tocopherol succinate is used as a vitamin E supplement with similar but differential activities compared to other esterified forms of vitamin E. Its antioxidant and radioprotective properties make it a valuable compound for research on oxidative stress, radiation biology, and nutritional supplementation.

In vitro experiments with D-α-Tocopherol succinate typically involve preparing stock solutions in ethanol or DMSO and diluting them in assay buffers or cell culture media. For antioxidant assays, the compound is incubated with free radical-generating systems, and the scavenging activity is measured. For cell-based studies, cells are treated with varying concentrations of the compound (1-100 µM) for 24-72 hours, and cell viability, oxidative stress markers, and signaling pathways are assessed. The compound's ability to induce granulocyte-colony stimulating factor can be measured in cell culture.

Cytotoxicity assay [1]
Cell Types: HEI-OC1 cell line
Tested Concentrations: 1-20 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: Cytotoxicity was Dramatically induced at the concentration of 20 μM and demonstrated higher cytotoxicity compared with 10 μM Potency.

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Cell viability assay[1]
Cell Types: HEI-OC1 Cell Line
Tested Concentrations: 10 μM
Incubation Duration: 48 hrs (hours)
Experimental Results: Cisplatin-induced increase in cell population. Inhibits cisplatin-induced necrosis, ROS production, and late-stage apoptosis. Reduces cleaved PARP and inhibits the expression of caspase-3 associated with cisplatin-induced apoptosis.

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Cytotoxicity assay[2]
Cell Types: TC-1 Tumor Cell
Tested Concentrations: 0, 25 and 50 μM
Incubation Duration: 18 hrs (hours)
Experimental Results: Displayed dose-dependent cytotoxicity and induced a higher percentage of necrotic TC-1 cells (while not apoptotic cells).
In vitro cell-based assays using D-α-Tocopherol succinate are performed in various cell lines to study its antioxidant and cytoprotective effects. Cells are treated with the compound at concentrations of 1-100 µM for 24-72 hours. Oxidative stress is induced using agents such as hydrogen peroxide or tert-butyl hydroperoxide. Cell viability is assessed using MTT or other cell viability assays. ROS levels are measured using fluorescent probes such as DCFH-DA. The compound's ability to protect cells from oxidative damage is assessed by measuring cell viability and ROS levels. The compound is typically dissolved in ethanol or DMSO and diluted in cell culture medium.

Animal/Disease Models: Six to eightweeks old female C57BL/6 mice bearing TC-1 tumor cells [2]
Doses: 1 and 2 mg/kg
Route of Administration: intraperitoneal (ip) injection; 1 and 2 mg/kg 3 times, spaced 2 days; 10 days to 14 days of TC-1 tumor cell injection
Experimental Results: tumor volume diminished, especially at the dose of 2 mg/kg.
In vivo animal experiments with D-α-Tocopherol succinate have been conducted in mice to study its radioprotective effects. The compound was administered orally or by injection, and its effects on radiation-induced damage were assessed. The induction of granulocyte-colony stimulating factor was measured as a marker of radioprotection. The compound's antioxidant effects were assessed by measuring oxidative stress markers in tissues. The compound's radioprotective effects were dose-dependent.

Absorption, Distribution and Excretion
_In addition to the information below, please refer to the drug information page for α-tocopherol acetate for further data as the chemical properties of α-tocopherol succinate are closely related to those of α-tocopherol acetate._ It is generally believed that α-tocopherol succinate will eventually be deesterified or cleaved to form α-tocopherol after entering the body. Therefore, its pharmacodynamics and pharmacokinetics are expected to be similar to those of α-tocopherol. 50% to 80% is absorbed via the gastrointestinal tract. _In addition to the information below, please refer to the drug information page for α-tocopherol acetate for further data as the chemical properties of α-tocopherol succinate are closely related to those of α-tocopherol acetate._ It is generally believed that α-tocopherol succinate will eventually be deesterified or cleaved to form α-tocopherol after entering the body. Therefore, its pharmacodynamics and pharmacokinetics are expected to be similar to those of α-tocopherol. In addition to the information below, please refer to the drug information page for α-tocopherol acetate for further information as the chemical properties of α-tocopherol succinate and α-tocopherol acetate are closely related. It is generally believed that α-tocopherol succinate will eventually be deesterified or cleaved after entering the body, thus generating α-tocopherol. Therefore, its pharmacodynamics and pharmacokinetics are expected to be similar to those of α-tocopherol.

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Metabolism/Metabolites
_In addition to the information below, please also refer to the drug information page for α-tocopherol acetate for more data, as the chemical properties of α-tocopherol succinate are closely related to those of α-tocopherol acetate. _It is generally believed that α-tocopherol succinate will eventually be deesterified or cleaved to α-tocopherol after entering the human body. Therefore, its pharmacodynamics and pharmacokinetics are expected to be similar to those of α-tocopherol. Hepatic metabolism.

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Biological Half-Life
_In addition to the information below, please also refer to the drug information page for α-tocopherol acetate for more data, as the chemical properties of α-tocopherol succinate are closely related to those of α-tocopherol acetate. _It is generally believed that α-tocopherol succinate will eventually be deesterified or cleaved to α-tocopherol after entering the human body. Therefore, its pharmacodynamics and pharmacokinetics are expected to be similar to those of α-tocopherol.
D-α-Tocopherol succinate has a molecular weight of 530.78 g/mol and the formula C33H54O5. The compound appears as an off-white to pale yellow solid. For storage, the compound is kept at room temperature in a dry place, protected from light. It is a fat-soluble vitamin E derivative and is used as a vitamin E supplement. The compound is a potent antioxidant and protects mice from gamma-radiation by induction of granulocyte-colony stimulating factor. It is also known as vitamin E succinate.

Protein Binding
In addition to the information below, please refer to the drug information page for α-tocopherol acetate for more data, as the chemical properties of α-tocopherol succinate and α-tocopherol acetate are closely related. It is generally believed that α-tocopherol succinate will eventually be deesterified or cleaved to form α-tocopherol after entering the body. Therefore, its pharmacodynamics and pharmacokinetics are expected to be similar to α-tocopherol. It binds to β-lipoproteins in the blood.
Specific toxicological data for D-α-Tocopherol succinate are not extensively provided. As a vitamin E derivative, it is generally considered to have low toxicity. However, at very high doses, vitamin E can have adverse effects. The compound is intended for research use only and is not for human consumption. Standard laboratory safety precautions should be followed when handling this compound, including the use of gloves and eye protection.

[1]. The effects of the antioxidant α-tocopherol succinate on cisplatin-induced ototoxicity in HEI-OC1 auditory cells. Int J Pediatr Otorhinolaryngol. 2016 Jul;86:9-14.

[2]. Treatment of tumors with vitamin E suppresses myeloid derived suppressor cells and enhances CD8+ T cell-mediated antitumor effects. PLoS One. 2014 Jul 29;9(7):e103562.

Pharmacodynamics
Of the eight different vitamin E variants, α-tocopherol is the predominant form of vitamin E in human and animal tissues and has the highest bioavailability. This is because the liver preferentially re-secretes α-tocopherol via the hepatic α-tocopherol transfer protein (α-TTP); the liver metabolizes and excretes all other vitamin E variants, which is why the concentrations of other forms of vitamin E besides α-tocopherol are ultimately lower in the blood and cells. Furthermore, the term α-tocopherol generally refers to a group of eight possible stereoisomers, and is often called racemic tocopherol because it is a racemic mixture of all eight stereoisomers. Of the eight stereoisomers, RRR-α-tocopherol (sometimes also called d-α-tocopherol) is the naturally occurring form of α-tocopherol, which is likely most accurately recognized by the α-tocopherol transport protein (α-TTP), and its systemic bioavailability has been reported to be approximately twice that of racemic tocopherol. Therefore, when discussing vitamin E (at least in the context of its use for health indications), it is usually (but not always) referring to RRR- or d-α-tocopherol. Furthermore, in the absence of other evidence to suggest otherwise, it is generally accepted that α-tocopherol succinate undergoes a plausible deesterification reaction in the gastrointestinal tract before being absorbed as free tocopherol.
D-α-Tocopherol succinate (CAS 4345-03-3) is a fat-soluble vitamin E derivative and the salt form of vitamin E. It has the molecular formula C33H54O5 and a molecular weight of 530.78 g/mol. The compound is a potent antioxidant that protects mice from gamma-radiation by induction of granulocyte-colony stimulating factor. D-α-Tocopherol succinate is a vitamin E supplement used along with other esterified forms as a vitamin E supplement with similar but differential activities. It appears as an off-white to pale yellow solid. The compound is intended for research use only.

C33H54O5

530.7789

530.397

C, 74.67; H, 10.25; O, 15.07

4345-03-3

59-02-9 (vitamin E);58-95-7 (acetate);17407-37-3 (Hemisuccinate);4345-03-3; 9002-96-4 (PEG 1000 succinate);

20353

Solid powder

1.0±0.1 g/cm3

625.8±55.0 °C at 760 mmHg

~76 °C(lit.)

187.0±25.0 °C

0.0±1.9 mmHg at 25°C

1.498

11.88

1

5

17

38

720

3

O1C2C(C([H])([H])[H])=C(C([H])([H])[H])C(=C(C([H])([H])[H])C=2C([H])([H])C([H])([H])[C@@]1(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[C@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[C@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])OC(C([H])([H])C([H])([H])C(=O)O[H])=O

IELOKBJPULMYRW-NJQVLOCASA-N

InChI=1S/C33H54O5/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-20-33(8)21-19-28-27(7)31(25(5)26(6)32(28)38-33)37-30(36)18-17-29(34)35/h22-24H,9-21H2,1-8H3,(H,34,35)/t23-,24-,33-/m1/s1

4-oxo-4-[[(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl]oxy]butanoic acid

D –α-Tocopherol Hemisuccinate; Vitamin E Succinate; Tocopherol succinate; D-α-Tocopherol Succinate

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 (~471.00 mM)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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