DrugBank: Vitamin E (DB00163)

targets (10) enzymes (8) carriers (1)

Identification

Name

Vitamin E

Accession Number

DB00163 (EXPT03227, NUTR00061)

Type

small molecule

Groups

approved, nutraceutical

Description

A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids. [PubChem]

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

alpha-Tocopherol
Tocopherol

Salts

Not Available

Brand names

Name	Company
Amino-Opti-E
Aquasol E
Daltose
E-200 I.U. Softgels
E-Complex-600
E-Ferol
E-Vitamin succinate
Gordo-Vite E
Vitamin Plus E Softgells
Vitec

Brand mixtures

Not Available

Categories

Dietary supplement
Micronutrient
Antioxidants
Vitamins/minerals
Vitamins

CAS number

59-02-9

Weight

Average: 430.7061
Monoisotopic: 430.381080844

Chemical Formula

C₂₉H₅₀O₂

InChI Key

InChIKey=GVJHHUAWPYXKBD-IEOSBIPESA-N

InChI

InChI=1S/C29H50O2/c1-20(2)12-9-13-21(3)14-10-15-22(4)16-11-18-29(8)19-17-26-25(7)27(30)23(5)24(6)28(26)31-29/h20-22,30H,9-19H2,1-8H3/t21-,22-,29-/m1/s1

Plain Text

IUPAC Name

(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-1-benzopyran-6-ol

SMILES

CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC[C@]1(C)CCC2=C(O1)C(C)=C(C)C(O)=C2C

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Tocopherols

Substructures

Tocopherols
Hydroxy Compounds
Pyrans
Phenols and Derivatives
Ethers
Benzene and Derivatives
Hydroquinones
Methoxyphenols
Benzopyrans
Heterocyclic compounds
Aromatic compounds
Anisoles
Phenyl Esters

Pharmacology

Indication

Vitamin E, known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.

Pharmacodynamics

Vitamin E has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Vitamin E is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Vitamin E is a fat-soluble vitamin and is an important antioxidant. It acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Vitamin E is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns. There are three specific situations when a vitamin E deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), and is seen in individuals with rare disorders of fat metabolism. A vitamin E deficiency is usually characterized by neurological problems due to poor nerve conduction. Symptoms may include infertility, neuromuscular impairment, menstrual problems, miscarriage and uterine degradation. Preliminary research has led to a widely held belief that vitamin E may help prevent or delay coronary heart disease. Antioxidants such as vitamin E help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of vitamin E have been linked to increased incidence of breast and colon cancer.

Mechanism of action

Although all forms of Vitamin E exhibit antioxidant activity, it is known that the antioxidant activity of vitamin E is not sufficient to explain the vitamin's biological activity.
Vitamin E's anti-atherogenic activity involves the inhibition of the oxidation of LDL and the accumulation of oxLDL in the arterial wall. It also appears to reduce oxLDL-induced apoptosis in human endothelial cells. Oxidation of LDL is a key early step in atherogenesis as it triggers a number of events which lead to the formation of atherosclerotic plaque. In addition, vitamin E inhibits protein kinase C (PKC) activity. PKC plays a role in smooth muscle cell proliferation, and, thus, the inhibition of PKC results in inhibition of smooth muscle cell proliferation, which is involved in atherogenesis.
Vitamin E's antithrombotic and anticoagulant activities involves the downregulation of the expression of intracellular cell adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 which lowers the adhesion of blood components to the endothelium. In addition, vitamin E upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase (COX)-1 which in turn enhances the release of prostacyclin. Prostacyclin is a vasodilating factor and inhibitor of platelet aggregation and platelet release. It is also known that platelet aggregation is mediated by a mechanism involving the binding of fibrinogen to the glycoprotein IIb/IIIa (GPIIb/IIIa) complex of platelets. GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet aggregation response. GPIIb is the alpha-subunit of this platelet membrane protein. Alpha-tocopherol downregulates GPIIb promoter activity which results in reduction of GPIIb protein expression and decreased platelet aggregation. Vitamin E has also been found in culture to decrease plasma production of thrombin, a protein which binds to platelets and induces aggregation. A metabolite of vitamin E called vitamin E quinone or alpha-tocopheryl quinone (TQ) is a potent anticoagulant. This metabolite inhibits vitamin K-dependent carboxylase, which is a major enzyme in the coagulation cascade.
The neuroprotective effects of vitamin E are explained by its antioxidant effects. Many disorders of the nervous system are caused by oxidative stress. Vitamin E protects against this stress, thereby protecting the nervouse system.
The immunomodulatory effects of Vitamin E have been demonstrated in vitro, where alpha-tocopherol increases mitogenic response of T lymphocytes from aged mice. The mechanism of this response by vitamin E is not well understood, however it has been suggested that vitamin E itself may have mitogenic activity independent of its antioxidant activity.
Lastly, the mechanism of action of vitamin E's antiviral effects (primarily against HIV-1) involves its antioxidant activity. Vitamin E reduces oxidative stress, which is thought to contribute to HIV-1 pathogenesis, as well as to the pathogenesis of other viral infections. Vitamin E also affects membrane integrity and fluidity and, since HIV-1 is a membraned virus, altering membrane fluidity of HIV-1 may interfere with its ability to bind to cell-receptor sites, thus decreasing its infectivity.

Absorption

50 to 80% absorbed from gastrointestinal tract.

Volume of distribution

Not Available

Protein binding

Bound to beta-lipoproteins in blood.

Metabolism

Hepatic.

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
Capsule	Oral
Cream	Topical
Liquid	Intramuscular
Liquid	Oral
Ointment	Topical
Powder	Oral
Tablet	Oral

Prices

Unit description	Cost	Unit
Vitamin e acetate liquid	1.07 USD	ml
Ester-e 400 unit softgel	0.26 USD	softgel capsule
Vit e nat'l blnd 1000 unit capsule	0.2 USD	capsule
Vitamin e 400 unit tablet	0.19 USD	tablet
E pherol 400 unit tablet	0.13 USD	tablet
Vitamin e 1000 unit capsule	0.13 USD	capsule
Vitamin e beauty oil	0.1 USD	ml
CVS Pharmacy vitamin e 800 unit softgel	0.09 USD	softgel capsule
Vitamin e 600 unit capsule	0.07 USD	capsule
Vitamin e 400 unit capsule	0.06 USD	capsule
CVS Pharmacy vitamin e 400 unit capsule	0.05 USD	capsule
Vitamin e 200 unit capsule	0.05 USD	each
CVS Pharmacy vitamin e 200 unit softgel	0.04 USD	softgel capsule
Natural vitamin e 400 unit cap	0.04 USD	capsule
Natural vitamin e 400 unit capsule	0.04 USD	capsule
Vitamin e 100 unit capsule	0.04 USD	capsule
Vitamin e 400 unit softgel	0.04 USD	softgel capsule
CVS Pharmacy vitamin e plus cream	0.03 USD	g
Natural vit e 200 unit capsule	0.03 USD	capsule
Vitamin e cream	0.02 USD	g

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

liquid

Experimental Properties

Property	Value	Source
melting point	3 °C	PhysProp
water solubility	Insoluble in water, but water-dispersible.	Not Available
logP	10	Not Available

Predicted Properties

Property	Value	Source
water solubility	7.04e-06 g/l	ALOGPS
logP	8.84	ALOGPS
logP	10.51	ChemAxon
logS	-7.8	ALOGPS
pKa (strongest acidic)	10.8	ChemAxon
pKa (strongest basic)	-4.9	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	2	ChemAxon
hydrogen donor count	1	ChemAxon
polar surface area	29.46	ChemAxon
rotatable bond count	12	ChemAxon
refractivity	135.37	ChemAxon
polarizability	55.29	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Iuliano L, Micheletta F, Maranghi M, Frati G, Diczfalusy U, Violi F: Bioavailability of vitamin E as function of food intake in healthy subjects: effects on plasma peroxide-scavenging activity and cholesterol-oxidation products. Arterioscler Thromb Vasc Biol. 2001 Oct;21(10):E34-7. Pubmed
Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E: Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10. Pubmed
Horwitt MK, Elliott WH, Kanjananggulpan P, Fitch CD: Serum concentrations of alpha-tocopherol after ingestion of various vitamin E preparations. Am J Clin Nutr. 1984 Aug;40(2):240-5. Pubmed
Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS: Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med. 2006 Apr 27;354(17):1796-806. Pubmed
Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH: Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet. 2006 Apr 8;367(9517):1145-54. Pubmed
Linus Pauling Institute Link

External Links

Resource	Link
KEGG Compound	C02477
PubChem Compound	14985
PubChem Substance	46506524
ChemSpider	14265
ChEBI	18145
ChEMBL	18145
PharmGKB	PA451900
HET	VIT
Drugs.com	http://www.drugs.com/vitamin_e.html
PDRhealth	http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/vit_0266.shtml
Wikipedia	http://en.wikipedia.org/wiki/Vitamin_E

ATC Codes

A11HA03

AHFS Codes

84:24.12
88:20.00

PDB Entries

1KPM

FDA label

Not Available

MSDS

show (74.1 KB)

Interactions

Drug Interactions

Drug	Interaction
Amprenavir	Increased serum levels of vitamin E
Orlistat	Orlistat may impair the absorption of vitamin E, a fat soluble vitamin. Oral vitamin E should be administered 2 hours prior to or post orlistat administration.

Food Interactions

Not Available

Targets
1. Nuclear receptor subfamily 1 group I member 2 Pharmacological action: unknown Orphan receptor; its natural ligand is probably pregnane. Binds to a response element in the CYP3A4 and ABCB1/MDR1 genes promoter. Activates its expression in response to a wide variety of endobiotics and xenobiotics Organism class: human UniProt ID: O75469 Gene: NR1I2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Rabovsky A, Cuomo J, Eich N: Measurement of plasma antioxidant reserve after supplementation with various antioxidants in healthy subjects. Clin Chim Acta. 2006 Sep;371(1-2):55-60. Epub 2006 Mar 6. Pubmed Meijerman I, Beijnen JH, Schellens JH: Herb-drug interactions in oncology: focus on mechanisms of induction. Oncologist. 2006 Jul-Aug;11(7):742-52. Pubmed 2. Protein kinase C beta type Pharmacological action: unknown This is a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme. PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters. May be considered as a novel component of the NF-kappa-B signaling axis responsible for the survival and activation of B-cells after BCR cross-linking Organism class: human UniProt ID: P05771 Gene: PRKCB1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Wigg SJ, Tare M, Forbes J, Cooper ME, Thomas MC, Coleman HA, Parkington HC, O’Brien RC: Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-beta in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats. Diabetologia. 2004 Jun;47(6):1038-46. Epub 2004 Jun 8. Pubmed Huang Y, Ishizuka T, Miura A, Kajita K, Ishizawa M, Kimura M, Yamamoto Y, Kawai Y, Morita H, Uno Y, Yasuda K: Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes. Diabetes Res Clin Pract. 2002 Mar;55(3):175-83. Pubmed Ganz MB, Seftel A: Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E. Am J Physiol Endocrinol Metab. 2000 Jan;278(1):E146-52. Pubmed 3. Arachidonate 5-lipoxygenase Pharmacological action: unknown Organism class: human UniProt ID: P09917 Gene: ALOX5 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. Pubmed 4. Protein kinase C alpha type Pharmacological action: unknown PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters Organism class: human UniProt ID: P17252 Gene: PRKCA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Azzi A, Boscoboinik D, Clement S, Marilley D, Ozer NK, Ricciarelli R, Tasinato A: Alpha-tocopherol as a modulator of smooth muscle cell proliferation. Prostaglandins Leukot Essent Fatty Acids. 1997 Oct;57(4-5):507-14. Pubmed Sylvester PW, McIntyre BS, Gapor A, Briski KP: Vitamin E inhibition of normal mammary epithelial cell growth is associated with a reduction in protein kinase C(alpha) activation. Cell Prolif. 2001 Dec;34(6):347-57. Pubmed Huang Y, Ishizuka T, Miura A, Kajita K, Ishizawa M, Kimura M, Yamamoto Y, Kawai Y, Morita H, Uno Y, Yasuda K: Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes. Diabetes Res Clin Pract. 2002 Mar;55(3):175-83. Pubmed 5. Diacylglycerol kinase alpha Pharmacological action: unknown Upon cell stimulation converts the second messenger diacylglycerol into phosphatidate, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity Organism class: human UniProt ID: P23743 Gene: DGKA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed 6. Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform Pharmacological action: unknown PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase Organism class: human UniProt ID: P62714 Gene: PPP2CB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed 7. Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform Pharmacological action: unknown PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Can dephosphorylate SV40 large T antigen and p53. Dephosphorylates SV40 large T antigen, preferentially on serine residues 120, 123, 677, and perhaps 679. The C subunit was most active, followed by the AC form, which was more active than the ABC form, and activity of all three forms was strongly stimulated by manganese, and to a lesser extent by magnesium. Dephosphorylation by the AC form, but not C or ABC form is inhibited by small T antigen Organism class: human UniProt ID: P67775 Gene: PPP2CA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed 8. SEC14-like protein 4 Pharmacological action: unknown Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids Organism class: human UniProt ID: Q9UDX3 Gene: SEC14L4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed 9. SEC14-like protein 3 Pharmacological action: unknown Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids Organism class: human UniProt ID: Q9UDX4 Gene: SEC14L3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Ye X, Ji C, Yin G, Tang R, Zeng L, Gu S, Ying K, Xie Y, Zhao RC, Mao Y: Characterization of a human Sec14-like protein cDNA SEC14L3 highly homologous to human SPF/TAP. Mol Biol Rep. 2004 Mar;31(1):59-63. Pubmed 10. SEC14-like protein 2 Pharmacological action: unknown Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinity to other tocopherols and to tocotrienols. May have a transcriptional activatory activity via its association with alpha-tocopherol. Probably recognizes and binds some squalene structure, suggesting that it may regulate cholesterol biosynthesis by increasing the transfer of squalene to a metabolic active pool in the cell Organism class: human UniProt ID: O76054 Gene: SEC14L2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Neuzil J, Dong LF, Wang XF, Zingg JM: Tocopherol-associated protein-1 accelerates apoptosis induced by alpha-tocopheryl succinate in mesothelioma cells. Biochem Biophys Res Commun. 2006 May 19;343(4):1113-7. Epub 2006 Mar 31. Pubmed Ni J, Pang ST, Yeh S: Differential retention of alpha-vitamin E is correlated with its transporter gene expression and growth inhibition efficacy in prostate cancer cells. Prostate. 2007 Apr 1;67(5):463-71. Pubmed

Targets

1. Nuclear receptor subfamily 1 group I member 2

Pharmacological action: unknown

Orphan receptor; its natural ligand is probably pregnane. Binds to a response element in the CYP3A4 and ABCB1/MDR1 genes promoter. Activates its expression in response to a wide variety of endobiotics and xenobiotics

Organism class: human
UniProt ID: O75469 Link_out

Gene: NR1I2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Rabovsky A, Cuomo J, Eich N: Measurement of plasma antioxidant reserve after supplementation with various antioxidants in healthy subjects. Clin Chim Acta. 2006 Sep;371(1-2):55-60. Epub 2006 Mar 6. Pubmed
Meijerman I, Beijnen JH, Schellens JH: Herb-drug interactions in oncology: focus on mechanisms of induction. Oncologist. 2006 Jul-Aug;11(7):742-52. Pubmed

2. Protein kinase C beta type

Pharmacological action: unknown

This is a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme. PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters. May be considered as a novel component of the NF-kappa-B signaling axis responsible for the survival and activation of B-cells after BCR cross-linking

Organism class: human
UniProt ID: P05771 Link_out

Gene: PRKCB1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Wigg SJ, Tare M, Forbes J, Cooper ME, Thomas MC, Coleman HA, Parkington HC, O’Brien RC: Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-beta in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats. Diabetologia. 2004 Jun;47(6):1038-46. Epub 2004 Jun 8. Pubmed
Huang Y, Ishizuka T, Miura A, Kajita K, Ishizawa M, Kimura M, Yamamoto Y, Kawai Y, Morita H, Uno Y, Yasuda K: Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes. Diabetes Res Clin Pract. 2002 Mar;55(3):175-83. Pubmed
Ganz MB, Seftel A: Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E. Am J Physiol Endocrinol Metab. 2000 Jan;278(1):E146-52. Pubmed

3. Arachidonate 5-lipoxygenase

Pharmacological action: unknown
Organism class: human
UniProt ID: P09917 Link_out

Gene: ALOX5 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. Pubmed

4. Protein kinase C alpha type

Pharmacological action: unknown

PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters

Organism class: human
UniProt ID: P17252 Link_out

Gene: PRKCA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Azzi A, Boscoboinik D, Clement S, Marilley D, Ozer NK, Ricciarelli R, Tasinato A: Alpha-tocopherol as a modulator of smooth muscle cell proliferation. Prostaglandins Leukot Essent Fatty Acids. 1997 Oct;57(4-5):507-14. Pubmed
Sylvester PW, McIntyre BS, Gapor A, Briski KP: Vitamin E inhibition of normal mammary epithelial cell growth is associated with a reduction in protein kinase C(alpha) activation. Cell Prolif. 2001 Dec;34(6):347-57. Pubmed
Huang Y, Ishizuka T, Miura A, Kajita K, Ishizawa M, Kimura M, Yamamoto Y, Kawai Y, Morita H, Uno Y, Yasuda K: Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes. Diabetes Res Clin Pract. 2002 Mar;55(3):175-83. Pubmed

5. Diacylglycerol kinase alpha

Pharmacological action: unknown

Upon cell stimulation converts the second messenger diacylglycerol into phosphatidate, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity

Organism class: human
UniProt ID: P23743 Link_out

Gene: DGKA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

6. Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform

Pharmacological action: unknown

PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase

Organism class: human
UniProt ID: P62714 Link_out

Gene: PPP2CB Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

7. Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform

Pharmacological action: unknown

PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Can dephosphorylate SV40 large T antigen and p53. Dephosphorylates SV40 large T antigen, preferentially on serine residues 120, 123, 677, and perhaps 679. The C subunit was most active, followed by the AC form, which was more active than the ABC form, and activity of all three forms was strongly stimulated by manganese, and to a lesser extent by magnesium. Dephosphorylation by the AC form, but not C or ABC form is inhibited by small T antigen

Organism class: human
UniProt ID: P67775 Link_out

Gene: PPP2CA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

8. SEC14-like protein 4

Pharmacological action: unknown

Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids

Organism class: human
UniProt ID: Q9UDX3 Link_out

Gene: SEC14L4 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

9. SEC14-like protein 3

Pharmacological action: unknown

Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids

Organism class: human
UniProt ID: Q9UDX4 Link_out

Gene: SEC14L3 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Ye X, Ji C, Yin G, Tang R, Zeng L, Gu S, Ying K, Xie Y, Zhao RC, Mao Y: Characterization of a human Sec14-like protein cDNA SEC14L3 highly homologous to human SPF/TAP. Mol Biol Rep. 2004 Mar;31(1):59-63. Pubmed

10. SEC14-like protein 2

Pharmacological action: unknown

Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinity to other tocopherols and to tocotrienols. May have a transcriptional activatory activity via its association with alpha-tocopherol. Probably recognizes and binds some squalene structure, suggesting that it may regulate cholesterol biosynthesis by increasing the transfer of squalene to a metabolic active pool in the cell

Organism class: human
UniProt ID: O76054 Link_out

Gene: SEC14L2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Neuzil J, Dong LF, Wang XF, Zingg JM: Tocopherol-associated protein-1 accelerates apoptosis induced by alpha-tocopheryl succinate in mesothelioma cells. Biochem Biophys Res Commun. 2006 May 19;343(4):1113-7. Epub 2006 Mar 31. Pubmed
Ni J, Pang ST, Yeh S: Differential retention of alpha-vitamin E is correlated with its transporter gene expression and growth inhibition efficacy in prostate cancer cells. Prostate. 2007 Apr 1;67(5):463-71. Pubmed

Enzymes
1. Glutathione S-transferase A2 Actions: inducer Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles UniProt ID: P09210 Gene: GSTA2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed 2. Glutathione S-transferase P Actions: inhibitor Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles UniProt ID: P09211 Gene: GSTP1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Ralat LA, Colman RF: Identification of tyrosine 79 in the tocopherol binding site of glutathione S-transferase pi. Biochemistry. 2006 Oct 17;45(41):12491-9. Pubmed 3. Glutathione transferase omega-1 Actions: inhibitor Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities UniProt ID: P78417 Gene: GSTO1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Sampayo-Reyes A, Zakharyan RA: Tocopherol esters inhibit human glutathione S-transferase omega. Acta Biochim Pol. 2006;53(3):547-52. Epub 2006 Oct 1. Pubmed 4. Glutathione S-transferase Mu 3 Actions: inducer Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May govern uptake and detoxification of both endogenous compounds and xenobiotics at the testis and brain blood barriers UniProt ID: P21266 Gene: GSTM3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Mustacich DJ, Gohil K, Bruno RS, Yan M, Leonard SW, Ho E, Cross CE, Traber MG: Alpha-tocopherol modulates genes involved in hepatic xenobiotic pathways in mice. J Nutr Biochem. 2009 Jun;20(6):469-76. Epub 2008 Sep 11. Pubmed 5. Glutamate--cysteine ligase catalytic subunit Actions: inducer UniProt ID: P48506 Gene: GCLC Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed 6. NAD(P)H dehydrogenase [quinone] 1 Actions: inducer The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis UniProt ID: P15559 Gene: NQO1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed 7. Heme oxygenase 1 Actions: inducer Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed UniProt ID: P09601 Gene: HMOX1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed 8. Superoxide dismutase [Cu-Zn] Actions: inducer Destroys radicals which are normally produced within the cells and which are toxic to biological systems UniProt ID: P00441 Gene: SOD1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed

Enzymes

1. Glutathione S-transferase A2

Actions: inducer

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

UniProt ID: P09210 Link_out

Gene: GSTA2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed

2. Glutathione S-transferase P

Actions: inhibitor

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

UniProt ID: P09211 Link_out

Gene: GSTP1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Ralat LA, Colman RF: Identification of tyrosine 79 in the tocopherol binding site of glutathione S-transferase pi. Biochemistry. 2006 Oct 17;45(41):12491-9. Pubmed

3. Glutathione transferase omega-1

Actions: inhibitor

Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities

UniProt ID: P78417 Link_out

Gene: GSTO1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Sampayo-Reyes A, Zakharyan RA: Tocopherol esters inhibit human glutathione S-transferase omega. Acta Biochim Pol. 2006;53(3):547-52. Epub 2006 Oct 1. Pubmed

4. Glutathione S-transferase Mu 3

Actions: inducer

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May govern uptake and detoxification of both endogenous compounds and xenobiotics at the testis and brain blood barriers

UniProt ID: P21266 Link_out

Gene: GSTM3 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Mustacich DJ, Gohil K, Bruno RS, Yan M, Leonard SW, Ho E, Cross CE, Traber MG: Alpha-tocopherol modulates genes involved in hepatic xenobiotic pathways in mice. J Nutr Biochem. 2009 Jun;20(6):469-76. Epub 2008 Sep 11. Pubmed

5. Glutamate--cysteine ligase catalytic subunit

Actions: inducer
UniProt ID: P48506 Link_out

Gene: GCLC Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed

6. NAD(P)H dehydrogenase [quinone] 1

Actions: inducer

The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis

UniProt ID: P15559 Link_out

Gene: NQO1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed

7. Heme oxygenase 1

Actions: inducer

Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed

UniProt ID: P09601 Link_out

Gene: HMOX1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed

8. Superoxide dismutase [Cu-Zn]

Actions: inducer

Destroys radicals which are normally produced within the cells and which are toxic to biological systems

UniProt ID: P00441 Link_out

Gene: SOD1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J: alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem. 2010 Dec;21(12):1222-31. Epub 2010 Feb 12. Pubmed

Carriers
1. Alpha-tocopherol transfer protein Binds alpha-tocopherol and enhances its transfer between separate membranes UniProt ID: P49638 Gene: TTPA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report

Comments

Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19