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].

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].

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).

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.

Absorption, Distribution and Excretion
_In addition to any following information, owing to alpha-Tocopherol succinate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ It is generally believed that alpha-tocopherol succinate is ultimately de-esterified or cleaved to provide alpha-tocopherol once administered to the human body. It is consequently expected that pharmacodynamics and pharmacokinetics similar to that of alpha-tocopherol to be followed. 50 to 80% absorbed from gastrointestinal tract.
_In addition to any following information, owing to alpha-Tocopherol succinate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ It is generally believed that alpha-tocopherol succinate is ultimately de-esterified or cleaved to provide alpha-tocopherol once administered to the human body. It is consequently expected that pharmacodynamics and pharmacokinetics similar to that of alpha-tocopherol to be followed.
_In addition to any following information, owing to alpha-Tocopherol succinate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ It is generally believed that alpha-tocopherol succinate is ultimately de-esterified or cleaved to provide alpha-tocopherol once administered to the human body. It is consequently expected that pharmacodynamics and pharmacokinetics similar to that of alpha-tocopherol to be followed.
_In addition to any following information, owing to alpha-Tocopherol succinate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ It is generally believed that alpha-tocopherol succinate is ultimately de-esterified or cleaved to provide alpha-tocopherol once administered to the human body. It is consequently expected that pharmacodynamics and pharmacokinetics similar to that of alpha-tocopherol to be followed.

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Metabolism / Metabolites
_In addition to any following information, owing to alpha-Tocopherol succinate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ It is generally believed that alpha-tocopherol succinate is ultimately de-esterified or cleaved to provide alpha-tocopherol once administered to the human body. It is consequently expected that pharmacodynamics and pharmacokinetics similar to that of alpha-tocopherol to be followed. Hepatic.

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Biological Half-Life
_In addition to any following information, owing to alpha-Tocopherol succinate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ It is generally believed that alpha-tocopherol succinate is ultimately de-esterified or cleaved to provide alpha-tocopherol once administered to the human body. It is consequently expected that pharmacodynamics and pharmacokinetics similar to that of alpha-tocopherol to be followed.

Protein Binding
_In addition to any following information, owing to alpha-Tocopherol succinate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ It is generally believed that alpha-tocopherol succinate is ultimately de-esterified or cleaved to provide alpha-tocopherol once administered to the human body. It is consequently expected that pharmacodynamics and pharmacokinetics similar to that of alpha-tocopherol to be followed. Bound to beta-lipoproteins in blood.

[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 separate variants of vitamin E, alpha-tocopherol is the predominant form of vitamin E in human and animal tissues, and it has the highest bioavailability. This is because the liver preferentially resecretes only alpha-tocopherol by way of the hepatic alpha-tocopherol transfer protein (alpha-TTP); the liver metabolizes and excretes all the other vitamin E variants, which is why blood and cellular concentrations of other forms of vitamin E other than alpha-tocopherol are ultimately lower. Furthermore, the term alpha-tocopherol generally refers to a group of eight possible stereoisomers which is often called all-rac-tocopherol for being a racemic mixture of all eight stereoisomers. Of the eight stereoisomers, the RRR-alpha-tocopherol - or sometimes referred to as the d-alpha-tocopherol - stereoisomer is the naturally occurring form of alpha-tocopherol that is perhaps best recognized by the alpha-TTP and has been reported to demonstrate approximately twice the systemic availability of all-rac-tocopherol. As a result, often times (but certainly not always) the discussion of vitamin E - at least within the context of using the vitamin for health-related indications - is generally in reference to the use of RRR- or d-alpha-tocopherol. Subsequently, without further evidence to suggest otherwise, alpha-tocpherol succinate is generally believed to undergo a logical de-esterification in the gastrointestinal tract before being subsequently absorbed as free tocopherol.

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.)