Identification

Name
Menadione
Accession Number
DB00170  (NUTR00062)
Type
Small Molecule
Groups
Approved, Nutraceutical
Description

A synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo. [PubChem]

Structure
Thumb
Synonyms
  • 2-Methyl-1,4-Naphthalenedione
  • 2-Methyl-1,4-naphthochinon
  • 2-Methyl-1,4-naphthoquinone
  • Menadione
  • Vitamin K3
Product Ingredients
IngredientUNIICASInChI Key
Menadiol diphosphateGRL65FEU3T84-98-0JTNHOVZOOVVGHI-UHFFFAOYSA-N
International/Other Brands
Synkavite
Categories
UNII
723JX6CXY5
CAS number
58-27-5
Weight
Average: 172.18
Monoisotopic: 172.0524295
Chemical Formula
C11H8O2
InChI Key
MJVAVZPDRWSRRC-UHFFFAOYSA-N
InChI
InChI=1S/C11H8O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6H,1H3
IUPAC Name
2-methyl-1,4-dihydronaphthalene-1,4-dione
SMILES
CC1=CC(=O)C2=CC=CC=C2C1=O

Pharmacology

Indication

The primary known function of vitamin K is to assist in the normal clotting of blood, but it may also play a role in normal bone calcification.

Structured Indications
Not Available
Pharmacodynamics

Menadione (Vitamin K3) is a fat-soluble vitamin precursor that is converted into menaquinone in the liver. Vitamin K1 and K2 are the naturally occurring types of vitamin K. The former, which is also known as phylloquinone, is synthesized by plants and can be found in such foods as spinach, broccoli, lettuce, and soybeans. The latter, sometimes alternatively referred to as menaquinone, is primarily produced by bacteria in the anterior part of the gut and the intestines. Vitamin K3, on the other hand, is one of the many manmade versions of vitamin K. Also called menadione, this yellowish, synthetic crystalline substance is converted into the active form of the K2 vitamin inside of the animal body. While a vitamin K deficiency can be dangerous, especially to infants that may easily suffer from extensive hemorrhaging, an overdose can be as equally detrimental. Newborns that are administered too great a dosage of vitamin K3 can suffer from kernicterus, a form of severe brain damage that may produce decreased movement, loss of appetite, seizures, deafness, mental retardation, and even death. This condition is associated with an abnormally high concentration of bilirubin, a bile pigment, in the tissues of the brain, which can be caused by the presence of K3. For this reason, K3 is less often utilized medically than it was in former times.

Mechanism of action

Menadione (vitamin K3) is involved as a cofactor in the posttranslational gamma-carboxylation of glutamic acid residues of certain proteins in the body. These proteins include the vitamin K-dependent coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor), X (Stuart factor), protein C, protein S, protein Zv and a growth-arrest-specific factor (Gas6). In contrast to the other vitamin K-dependent proteins in the blood coagulation cascade, protein C and protein S serve anticoagulant roles. The two vitamin K-dependent proteins found in bone are osteocalcin, also known as bone G1a (gamma-carboxyglutamate) protein or BGP, and the matrix G1a protein or MGP. Gamma-carboxylation is catalyzed by the vitamin K-dependent gamma-carboxylases. The reduced form of vitamin K, vitamin K hydroquinone, is the actual cofactor for the gamma-carboxylases. Proteins containing gamma-carboxyglutamate are called G1a proteins.

TargetActionsOrganism
AVitamin K-dependent gamma-carboxylase
cofactor
Human
AVitamin K epoxide reductase complex subunit 1
cofactor
Human
AVitamin K epoxide reductase complex subunit 1-like protein 1
cofactor
Human
UProthrombin
activator
Human
UCoagulation factor VII
activator
Human
UCoagulation factor IX
activator
Human
UCoagulation factor X
activator
Human
UVitamin K-dependent protein C
activator
Human
UVitamin K-dependent protein S
activator
Human
UVitamin K-dependent protein Z
activator
Human
URibosyldihydronicotinamide dehydrogenase [quinone]Not AvailableHuman
UNAD(P)H dehydrogenase [quinone] 1Not AvailableHuman
UOsteocalcin
agonist
Human
Absorption

Variable and ranges from 10% to 80%

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Menadione (vitamin K3), which is not used as a nutritional supplemental form of vitamin K for humans, has been reported to cause adverse reactions, including hemolytic anemia. Large doses have also been reported to cause brain damage.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Menadione can be increased when it is combined with Abiraterone.Approved
ArtesunateThe serum concentration of the active metabolites of Artesunate can be reduced when Artesunate is used in combination with Menadione resulting in a loss in efficacy.Approved
AzithromycinThe metabolism of Menadione can be decreased when combined with Azithromycin.Approved
BortezomibThe metabolism of Menadione can be decreased when combined with Bortezomib.Approved, Investigational
CaffeineThe metabolism of Menadione can be decreased when combined with Caffeine.Approved
CitalopramThe metabolism of Menadione can be decreased when combined with Citalopram.Approved
ClotrimazoleThe metabolism of Menadione can be decreased when combined with Clotrimazole.Approved, Vet Approved
Cyproterone acetateThe serum concentration of Menadione can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DeferasiroxThe serum concentration of Menadione can be increased when it is combined with Deferasirox.Approved, Investigational
DosulepinThe metabolism of Menadione can be decreased when combined with Dosulepin.Approved
Fibrinogen HumanThe risk or severity of adverse effects can be increased when Menadione is combined with Fibrinogen Human.Approved
FluvoxamineThe metabolism of Menadione can be decreased when combined with Fluvoxamine.Approved, Investigational
IsoniazidThe metabolism of Menadione can be decreased when combined with Isoniazid.Approved
LidocaineThe metabolism of Menadione can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Menadione can be decreased when combined with Lobeglitazone.Approved
MexiletineThe metabolism of Menadione can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Menadione can be decreased when combined with Midostaurin.Approved
NevirapineThe metabolism of Menadione can be decreased when combined with Nevirapine.Approved
NicotineThe metabolism of Menadione can be decreased when combined with Nicotine.Approved
OsimertinibThe serum concentration of Menadione can be decreased when it is combined with Osimertinib.Approved
Peginterferon alfa-2bThe serum concentration of Menadione can be increased when it is combined with Peginterferon alfa-2b.Approved
RopiniroleThe metabolism of Menadione can be decreased when combined with Ropinirole.Approved, Investigational
SimeprevirThe metabolism of Menadione can be decreased when combined with Simeprevir.Approved
Tenofovir disoproxilThe metabolism of Menadione can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Menadione can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Menadione can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Menadione can be decreased when combined with Ticlopidine.Approved
TretinoinTretinoin may increase the thrombogenic activities of Menadione.Approved, Investigational, Nutraceutical
VemurafenibThe serum concentration of Menadione can be increased when it is combined with Vemurafenib.Approved
ZucapsaicinThe metabolism of Menadione can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Joachim U. Schneider, Hans Kiefer, "Menadione choline bisulfite adduct, its preparation and antihemorrhagic compositions." U.S. Patent US4735969, issued January, 1980.

US4735969
General References
Not Available
External Links
Human Metabolome Database
HMDB01892
KEGG Drug
D02335
KEGG Compound
C05377
PubChem Compound
4055
PubChem Substance
46505447
ChemSpider
3915
BindingDB
24778
ChEBI
28869
ChEMBL
CHEMBL590
Therapeutic Targets Database
DNC001501
PharmGKB
PA450358
IUPHAR
2771
Guide to Pharmacology
GtP Drug Page
HET
VK3
PDRhealth
PDRhealth Drug Page
Wikipedia
Menadione
ATC Codes
B02BA02 — Menadione
AHFS Codes
Not Available
PDB Entries
1tuv / 2qr2 / 4f8y
FDA label
Not Available
MSDS
Download (52.9 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Menadione powder5.59USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)107 °CPhysProp
water solubility160 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.20HANSCH,C ET AL. (1995)
logS-3.03ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.504 mg/mLALOGPS
logP1.91ALOGPS
logP1.89ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)12.94ChemAxon
pKa (Strongest Basic)-7.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity50.54 m3·mol-1ChemAxon
Polarizability17.64 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8265
Caco-2 permeable+0.8641
P-glycoprotein substrateNon-substrate0.5245
P-glycoprotein inhibitor IInhibitor0.7375
P-glycoprotein inhibitor IINon-inhibitor0.8743
Renal organic cation transporterNon-inhibitor0.8027
CYP450 2C9 substrateNon-substrate0.7596
CYP450 2D6 substrateNon-substrate0.8924
CYP450 3A4 substrateNon-substrate0.5705
CYP450 1A2 substrateInhibitor0.934
CYP450 2C9 inhibitorInhibitor0.9165
CYP450 2D6 inhibitorInhibitor0.7999
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.7529
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8612
Ames testAMES toxic0.9108
CarcinogenicityNon-carcinogens0.9137
BiodegradationNot ready biodegradable0.7581
Rat acute toxicity2.7195 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.778
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.97 KB)
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MSGC-MSsplash10-0gk9-3900000000-ad6c0e599173ba802f73
GC-MS Spectrum - GC-MSGC-MSsplash10-0ufr-2910000000-bbd6cf78055e623046a6
GC-MS Spectrum - GC-MSGC-MSsplash10-0ufr-2910000000-5db665917b8c152a80b2
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0g4i-6900000000-0c6c7737ff416205089c
GC-MS Spectrum - GC-MSGC-MSsplash10-0gk9-3900000000-ad6c0e599173ba802f73
GC-MS Spectrum - GC-MSGC-MSsplash10-0ufr-2910000000-bbd6cf78055e623046a6
GC-MS Spectrum - GC-MSGC-MSsplash10-0ufr-2910000000-5db665917b8c152a80b2
Mass Spectrum (Electron Ionization)MSsplash10-0gk9-5900000000-48fb5ac08ce624a689cc
MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)LC-MS/MSsplash10-074j-1900000000-a62dd17c23ac6e7fa95d
MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)LC-MS/MSsplash10-0aor-1900000000-ce35b89eaf766c9398e8
MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)LC-MS/MSsplash10-004i-9100000000-65a9c21d7aa7be21de3a
MS/MS Spectrum - EI-B (HITACHI M-80) , PositiveLC-MS/MSsplash10-0g4i-6900000000-0c6c7737ff416205089c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-ea17be197704c13eba82
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-2900000000-2d0b65ea01fe9dd6b4fe
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-7900000000-509fb00927321d93a529
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-252f2831b39763f805b4
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-cea08e3f258cdd275a55
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00dr-6900000000-b84149529316a1f0987f
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-1900000000-b489978f8a44b156f0f3
1H NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as naphthoquinones. These are compounds containing a naphthohydroquinone moiety, which consists of a benzene ring linearly fused to a bezene-1,4-dione (quinone).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Naphthalenes
Sub Class
Naphthoquinones
Direct Parent
Naphthoquinones
Alternative Parents
Quinones / Aryl ketones / Organic oxides / Hydrocarbon derivatives
Substituents
Naphthoquinone / Aryl ketone / Quinone / Ketone / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound / Aromatic homopolycyclic compound
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
naphthoquinone (CHEBI:28869) / vitamin K, Fat-soluble vitamins (C05377) / a vitamin K (CPD-3766)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Gamma-glutamyl carboxylase activity
Specific Function
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vit...
Gene Name
GGCX
Uniprot ID
P38435
Uniprot Name
Vitamin K-dependent gamma-carboxylase
Molecular Weight
87560.065 Da
References
  1. Wang Z, Wang M, Finn F, Carr BI: The growth inhibitory effects of vitamins K and their actions on gene expression. Hepatology. 1995 Sep;22(3):876-82. [PubMed:7657295]
  2. Stafford DW: The vitamin K cycle. J Thromb Haemost. 2005 Aug;3(8):1873-8. [PubMed:16102054]
  3. Presnell SR, Stafford DW: The vitamin K-dependent carboxylase. Thromb Haemost. 2002 Jun;87(6):937-46. [PubMed:12083499]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Vitamin-k-epoxide reductase (warfarin-sensitive) activity
Specific Function
Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the...
Gene Name
VKORC1
Uniprot ID
Q9BQB6
Uniprot Name
Vitamin K epoxide reductase complex subunit 1
Molecular Weight
18234.3 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
  3. Oldenburg J, Bevans CG, Muller CR, Watzka M: Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle. Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):347-53. [PubMed:16677080]
  4. Stafford DW: The vitamin K cycle. J Thromb Haemost. 2005 Aug;3(8):1873-8. [PubMed:16102054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Vitamin-k-epoxide reductase (warfarin-sensitive) activity
Specific Function
Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K (in vitro), and may contribute to vitamin K-mediated protection against oxidative stress. Plays a rol...
Gene Name
VKORC1L1
Uniprot ID
Q8N0U8
Uniprot Name
Vitamin K epoxide reductase complex subunit 1-like protein 1
Molecular Weight
19835.425 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
  3. Oldenburg J, Bevans CG, Muller CR, Watzka M: Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle. Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):347-53. [PubMed:16677080]
  4. Stafford DW: The vitamin K cycle. J Thromb Haemost. 2005 Aug;3(8):1873-8. [PubMed:16102054]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Thrombospondin receptor activity
Specific Function
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
Gene Name
F2
Uniprot ID
P00734
Uniprot Name
Prothrombin
Molecular Weight
70036.295 Da
References
  1. Lee SK, Lee JY, Lee MY, Chung SM, Chung JH: Advantages of calcium green-1 over other fluorescent dyes in measuring cytosolic calcium in platelets. Anal Biochem. 1999 Sep 10;273(2):186-91. [PubMed:10469489]
  2. Casper HH, Alstad AD, Tacke DB, Johnson LJ, Lloyd WE: Evaluation of vitamin K3 feed additive for prevention of sweet clover disease. J Vet Diagn Invest. 1989 Apr;1(2):116-9. [PubMed:2484931]
  3. McCarthy DJ, Lindamood C 3rd, Gundberg CM, Hill DL: Retinoid-induced hemorrhaging and bone toxicity in rats fed diets deficient in vitamin K. Toxicol Appl Pharmacol. 1989 Feb;97(2):300-10. [PubMed:2922761]
  4. Szejtli J, Bolla-Pusztai E, Tardy-Lengyel M, Szabo P, Ferenczy T: Preparation, properties and biological activity of beta-cyclodextrin inclusion complex of menadione. Pharmazie. 1983 Mar;38(3):189-93. [PubMed:6867080]
  5. Wang Z, Wang M, Finn F, Carr BI: The growth inhibitory effects of vitamins K and their actions on gene expression. Hepatology. 1995 Sep;22(3):876-82. [PubMed:7657295]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Serine-type peptidase activity
Specific Function
Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, o...
Gene Name
F7
Uniprot ID
P08709
Uniprot Name
Coagulation factor VII
Molecular Weight
51593.465 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Serine-type endopeptidase activity
Specific Function
Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholi...
Gene Name
F9
Uniprot ID
P00740
Uniprot Name
Coagulation factor IX
Molecular Weight
51778.11 Da
References
  1. Berkessel A, Guixa M, Schmidt F, Neudorfl JM, Lex J: Highly enantioselective epoxidation of 2-methylnaphthoquinone (vitamin K3) mediated by new cinchona alkaloid phase-transfer catalysts. Chemistry. 2007;13(16):4483-98. [PubMed:17348045]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Serine-type endopeptidase activity
Specific Function
Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
Gene Name
F10
Uniprot ID
P00742
Uniprot Name
Coagulation factor X
Molecular Weight
54731.255 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Serine-type endopeptidase activity
Specific Function
Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts ...
Gene Name
PROC
Uniprot ID
P04070
Uniprot Name
Vitamin K-dependent protein C
Molecular Weight
52070.82 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
  3. Milgrom E, Diab H, Middleton F, Kane PM: Loss of vacuolar proton-translocating ATPase activity in yeast results in chronic oxidative stress. J Biol Chem. 2007 Mar 9;282(10):7125-36. Epub 2007 Jan 10. [PubMed:17215245]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Endopeptidase inhibitor activity
Specific Function
Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.
Gene Name
PROS1
Uniprot ID
P07225
Uniprot Name
Vitamin K-dependent protein S
Molecular Weight
75121.905 Da
References
  1. Chai YC, Hendrich S, Thomas JA: Protein S-thiolation in hepatocytes stimulated by t-butyl hydroperoxide, menadione, and neutrophils. Arch Biochem Biophys. 1994 Apr;310(1):264-72. [PubMed:8161215]
  2. Mallis RJ, Hamann MJ, Zhao W, Zhang T, Hendrich S, Thomas JA: Irreversible thiol oxidation in carbonic anhydrase III: protection by S-glutathiolation and detection in aging rats. Biol Chem. 2002 Mar-Apr;383(3-4):649-62. [PubMed:12033454]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Serine-type endopeptidase activity
Specific Function
Appears to assist hemostasis by binding thrombin and promoting its association with phospholipid vesicles. Inhibits activity of the coagulation protease factor Xa in the presence of SERPINA10, calc...
Gene Name
PROZ
Uniprot ID
P22891
Uniprot Name
Vitamin K-dependent protein Z
Molecular Weight
44743.605 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Nadph dehydrogenase (quinone) activity
Specific Function
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vi...
Gene Name
NQO2
Uniprot ID
P16083
Uniprot Name
Ribosyldihydronicotinamide dehydrogenase [quinone]
Molecular Weight
25918.4 Da
References
  1. Long DJ 2nd, Iskander K, Gaikwad A, Arin M, Roop DR, Knox R, Barrios R, Jaiswal AK: Disruption of dihydronicotinamide riboside:quinone oxidoreductase 2 (NQO2) leads to myeloid hyperplasia of bone marrow and decreased sensitivity to menadione toxicity. J Biol Chem. 2002 Nov 29;277(48):46131-9. Epub 2002 Sep 25. [PubMed:12351651]
  2. Kwiek JJ, Haystead TA, Rudolph J: Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry. 2004 Apr 20;43(15):4538-47. [PubMed:15078100]
  3. Foster CE, Bianchet MA, Talalay P, Zhao Q, Amzel LM: Crystal structure of human quinone reductase type 2, a metalloflavoprotein. Biochemistry. 1999 Aug 3;38(31):9881-6. [PubMed:10433694]
  4. Celli CM, Tran N, Knox R, Jaiswal AK: NRH:quinone oxidoreductase 2 (NQO2) catalyzes metabolic activation of quinones and anti-tumor drugs. Biochem Pharmacol. 2006 Jul 28;72(3):366-76. Epub 2006 May 4. [PubMed:16765324]
  5. Boutin JA, Chatelain-Egger F, Vella F, Delagrange P, Ferry G: Quinone reductase 2 substrate specificity and inhibition pharmacology. Chem Biol Interact. 2005 Feb 10;151(3):213-28. [PubMed:15733542]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Superoxide dismutase activity
Specific Function
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 vit...
Gene Name
NQO1
Uniprot ID
P15559
Uniprot Name
NAD(P)H dehydrogenase [quinone] 1
Molecular Weight
30867.405 Da
References
  1. Munday R, Smith BL, Munday CM: Effect of butylated hydroxyanisole on the toxicity of 2-hydroxy-1,4-naphthoquinone to rats. Chem Biol Interact. 1999 Feb 12;117(3):241-56. [PubMed:10190578]
  2. Chiou TJ, Wang YT, Tzeng WF: DT-diaphorase protects against menadione-induced oxidative stress. Toxicology. 1999 Nov 29;139(1-2):103-10. [PubMed:10614691]
  3. Munday R, Smith BL, Munday CM: Effect of inducers of DT-diaphorase on the toxicity of 2-methyl- and 2-hydroxy-1,4-naphthoquinone to rats. Chem Biol Interact. 1999 Dec 15;123(3):219-37. [PubMed:10654840]
  4. Ip SP, Yiu HY, Ko KM: Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT-diaphorase activity. Mol Cell Biochem. 2000 May;208(1-2):151-5. [PubMed:10939639]
  5. Kishi T, Takahashi T, Mizobuchi S, Mori K, Okamoto T: Effect of dicumarol, a Nad(P)h: quinone acceptor oxidoreductase 1 (DT-diaphorase) inhibitor on ubiquinone redox cycling in cultured rat hepatocytes. Free Radic Res. 2002 Apr;36(4):413-9. [PubMed:12069105]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Structural molecule activity
Specific Function
Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium.
Gene Name
BGLAP
Uniprot ID
P02818
Uniprot Name
Osteocalcin
Molecular Weight
10962.445 Da
References
  1. Price PA: Role of vitamin-K-dependent proteins in bone metabolism. Annu Rev Nutr. 1988;8:565-83. [PubMed:3060178]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Yee SB, Pritsos CA: Comparison of oxygen radical generation from the reductive activation of doxorubicin, streptonigrin, and menadione by xanthine oxidase and xanthine dehydrogenase. Arch Biochem Biophys. 1997 Nov 15;347(2):235-41. [PubMed:9367530]
Details
2. Aldehyde oxidase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xanthine dehydrogenase activity
Specific Function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name
AOX1
Uniprot ID
Q06278
Uniprot Name
Aldehyde oxidase
Molecular Weight
147916.735 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein complex binding
Specific Function
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
Gene Name
MTHFR
Uniprot ID
P42898
Uniprot Name
Methylenetetrahydrofolate reductase
Molecular Weight
74595.895 Da
References
  1. Vanoni MA, Ballou DP, Matthews RG: Methylenetetrahydrofolate reductase. Steady state and rapid reaction studies on the NADPH-methylenetetrahydrofolate, NADPH-menadione, and methyltetrahydrofolate-menadione oxidoreductase activities of the enzyme. J Biol Chem. 1983 Oct 10;258(19):11510-4. [PubMed:6352699]
  2. Clark JE, Ljungdahl LG: Purification and properties of 5,10-methylenetetrahydrofolate reductase, an iron-sulfur flavoprotein from Clostridium formicoaceticum. J Biol Chem. 1984 Sep 10;259(17):10845-9. [PubMed:6381490]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:32