Menadione

Identification

Generic Name
Menadione
DrugBank Accession Number
DB00170
Background

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

Type
Small Molecule
Groups
Approved, Nutraceutical
Structure
Weight
Average: 172.18
Monoisotopic: 172.0524295
Chemical Formula
C11H8O2
Synonyms
  • 2-Methyl-1,4-Naphthalenedione
  • 2-Methyl-1,4-naphthochinon
  • 2-Methyl-1,4-naphthoquinone
  • Menadione
  • Vitamin K 3
  • Vitamin K3
External IDs
  • USAF EK-5185

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.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofFactor ii deficiency•••••••••••••••••••• •••••••••• ••• ••••••••• •• ••••••• ••••••••••• ••••••••
Treatment ofVitamin b12 deficiency•••••••••••••••••••••
Contraindications & Blackbox Warnings
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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
Humans
AVitamin K epoxide reductase complex subunit 1
cofactor
Humans
AVitamin K epoxide reductase complex subunit 1-like protein 1
cofactor
Humans
UProthrombin
activator
Humans
UCoagulation factor IX
activator
Humans
UVitamin K-dependent protein C
activator
Humans
UVitamin K-dependent protein S
activator
Humans
URibosyldihydronicotinamide dehydrogenase [quinone]Not AvailableHumans
UNAD(P)H dehydrogenase [quinone] 1Not AvailableHumans
UOsteocalcin
agonist
Humans
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

Adverse Effects
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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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Albutrepenonacog alfaMenadione may increase the thrombogenic activities of Albutrepenonacog alfa.
Alpha-1-proteinase inhibitorAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Menadione.
AlteplaseThe therapeutic efficacy of Menadione can be decreased when used in combination with Alteplase.
Aminocaproic acidMenadione may increase the thrombogenic activities of Aminocaproic acid.
Andexanet alfaMenadione may increase the thrombogenic activities of Andexanet alfa.
Food Interactions
Not Available

Products

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International/Other Brands
Synkavite
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
LIBAVIT-K 20 MG AMPUL, 5 ADETMenadione (20 mg/2ml) + Sodium bisulfite (6 mg/2ml) + Sodium chloride (12.6 mg/2ml)Injection, solutionLİBA LABORATUARLARI A.Ş.1980-09-22Not applicableTurkey flag

Categories

ATC Codes
B02BA02 — Menadione
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aromatic homopolycyclic compound / Aryl ketone / Hydrocarbon derivative / Ketone / Naphthoquinone / Organic oxide / Organic oxygen compound / Organooxygen compound / Quinone
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
naphthoquinone (CHEBI:28869) / vitamin K, Fat-soluble vitamins (C05377) / a vitamin K (CPD-3766)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
723JX6CXY5
CAS number
58-27-5
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

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
Human Metabolome Database
HMDB0001892
KEGG Drug
D02335
KEGG Compound
C05377
PubChem Compound
4055
PubChem Substance
46505447
ChemSpider
3915
BindingDB
24778
RxNav
6728
ChEBI
28869
ChEMBL
CHEMBL590
ZINC
ZINC000000001677
Therapeutic Targets Database
DNC001501
PharmGKB
PA450358
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
VK3
PDRhealth
PDRhealth Drug Page
Wikipedia
Menadione
PDB Entries
1tuv / 2qr2 / 4f8y / 6rvh / 7uur / 8dqv
MSDS
Download (52.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentEGFR Inhibitor-associated Rash1
1SuspendedOtherCrohn's Disease (CD) / Ulcerative Colitis1
Not AvailableActive Not RecruitingTreatmentDermatologic Complications / Malignant Neoplasm / Pain1

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
  • Spectrum Pharmaceuticals
Dosage Forms
FormRouteStrength
Injection, solution
Injection, solution10 mg/2mL
Injection, solution
Injection, solution20 mg/2mL
Solution10 mg/1ml
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 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-MSsplash10-006x-1900000000-3c2bf459bf04eae7701d
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00di-1900000000-b489978f8a44b156f0f3
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-1900000000-b489978f8a44b156f0f3
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-361c4cf2f19bcf61c072
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-ea147ad168353e6a35fc
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-05fr-0900000000-88e8b91f240adc5ebaf3
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-95e539d9cde958e61fa6
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-014l-9000000000-be43df3bde24f019b2a9
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-4900000000-e796bda86ef9878625f8
1H NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-139.6017588
predicted
DarkChem Lite v0.1.0
[M-H]-139.4543588
predicted
DarkChem Lite v0.1.0
[M-H]-139.7296588
predicted
DarkChem Lite v0.1.0
[M-H]-139.5818588
predicted
DarkChem Lite v0.1.0
[M-H]-139.4926588
predicted
DarkChem Lite v0.1.0
[M-H]-128.8549
predicted
DeepCCS 1.0 (2019)
[M+H]+140.0662588
predicted
DarkChem Lite v0.1.0
[M+H]+137.6927821
predicted
DarkChem Standard v0.1.0
[M+H]+140.1577588
predicted
DarkChem Lite v0.1.0
[M+H]+140.0669588
predicted
DarkChem Lite v0.1.0
[M+H]+140.1286588
predicted
DarkChem Lite v0.1.0
[M+H]+132.6419
predicted
DeepCCS 1.0 (2019)
[M+Na]+139.5721588
predicted
DarkChem Lite v0.1.0
[M+Na]+139.7464588
predicted
DarkChem Lite v0.1.0
[M+Na]+139.6784588
predicted
DarkChem Lite v0.1.0
[M+Na]+139.6576588
predicted
DarkChem Lite v0.1.0
[M+Na]+139.6165588
predicted
DarkChem Lite v0.1.0
[M+Na]+141.77281
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
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. [Article]
  2. Stafford DW: The vitamin K cycle. J Thromb Haemost. 2005 Aug;3(8):1873-8. [Article]
  3. Presnell SR, Stafford DW: The vitamin K-dependent carboxylase. Thromb Haemost. 2002 Jun;87(6):937-46. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
  2. Stafford DW: The vitamin K cycle. J Thromb Haemost. 2005 Aug;3(8):1873-8. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
  2. Stafford DW: The vitamin K cycle. J Thromb Haemost. 2005 Aug;3(8):1873-8. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  2. Chiou TJ, Wang YT, Tzeng WF: DT-diaphorase protects against menadione-induced oxidative stress. Toxicology. 1999 Nov 29;139(1-2):103-10. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
Menadione was shown to inhibit CYP1A2 activity in vitro by a noncompetitive mechanism, possibly involving redox cycling (IC50 of 4.51 ± 0.57 μM). In vivo, menadione also affects CYP1A2 transcriptional expression. The clinical significance of these observations is unknown.
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. Sidorova YA, Grishanova AY, Lyakhovich VV: Rat hepatic CYP1A1 and CYP1A2 induction by menadione. Toxicol Lett. 2005 Feb 15;155(2):253-8. doi: 10.1016/j.toxlet.2004.10.001. [Article]
  2. Katsanou ES, Kyriakopoulou K, Emmanouil C, Fokialakis N, Skaltsounis AL, Machera K: Modulation of CYP1A1 and CYP1A2 hepatic enzymes after oral administration of Chios mastic gum to male Wistar rats. PLoS One. 2014 Jun 20;9(6):e100190. doi: 10.1371/journal.pone.0100190. eCollection 2014. [Article]
  3. Sidorova YA, Perepechaeva ML, Pivovarova EN, Markel AL, Lyakhovich VV, Grishanova AY: Menadione Suppresses Benzo(alpha)pyrene-Induced Activation of Cytochromes P450 1A: Insights into a Possible Molecular Mechanism. PLoS One. 2016 May 11;11(5):e0155135. doi: 10.1371/journal.pone.0155135. eCollection 2016. [Article]
  4. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
One study demonstrated that menadione inhibited CYP2A6 with an IC50 value of 8.01 ± 0.62 µM. The clinical significance of this observation is unknown.
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. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  2. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP1B1 in vitro with an IC50 of 7.02 ± 0.53 μM. The clinical significance of this observation is unknown.
General Function
Oxygen binding
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
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP2B6 in vitro with an IC50 of 5.76 ± 0.78 μM. The clinical significance of this observation is unknown.
General Function
Steroid 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
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP2C8 in vitro with an IC50 of 2.36 ± 0.11 μM. The clinical significance of this observation is unknown.
General Function
Steroid 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
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP2C9 in vitro with an IC50 of 8.91 ± 0.57 μM. The clinical significance of this observation is unknown.
General Function
Steroid 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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP2C19 in vitro with an IC50 of 8.51 ± 0.38 μM. The clinical significance of this observation is unknown.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP2D6 in vitro with an IC50 of 4.60 ± 0.87 μM. The clinical significance of this observation is unknown.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP2E1 in vitro with an IC50 of 5.58 ± 1.22 μM. The clinical significance of this observation is unknown.
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. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP3A4 in vitro with an IC50 of 8.24 ± 0.71 μM. The clinical significance of this observation is unknown.
General Function
Vitamin d3 25-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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP3A5 in vitro with an IC50 of 9.77 ± 3.33 μM. The clinical significance of this observation is unknown.
General Function
Oxygen binding
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
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Menadione inhibits CYP3A7 in vitro with an IC50 of 5.92 ± 0.81 μM. The clinical significance of this observation is unknown.
General Function
Oxygen binding
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Details
14. Aldehyde oxidase
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
Menadione was shown to inhibit CYP1A1 activity in vitro by a noncompetitive mechanism, possibly involving redox cycling (IC50 of 4.39 ± 0.42 μM). In vivo, menadione also affects CYP1A1 transcriptional expression. The clinical significance of these observations is unknown.
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. Sidorova YA, Grishanova AY: Dose- and time-dependent effects of menadione on enzymes of xenobiotic metabolism in rat liver. Bull Exp Biol Med. 2004 Mar;137(3):231-4. doi: 10.1023/b:bebm.0000031556.47763.04. [Article]
  2. Sidorova YA, Grishanova AY, Lyakhovich VV: Rat hepatic CYP1A1 and CYP1A2 induction by menadione. Toxicol Lett. 2005 Feb 15;155(2):253-8. doi: 10.1016/j.toxlet.2004.10.001. [Article]
  3. Sidorova YA, Perepechaeva ML, Pivovarova EN, Markel AL, Lyakhovich VV, Grishanova AY: Menadione Suppresses Benzo(alpha)pyrene-Induced Activation of Cytochromes P450 1A: Insights into a Possible Molecular Mechanism. PLoS One. 2016 May 11;11(5):e0155135. doi: 10.1371/journal.pone.0155135. eCollection 2016. [Article]
  4. Jan YH, Richardson JR, Baker AA, Mishin V, Heck DE, Laskin DL, Laskin JD: Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication. Toxicol Appl Pharmacol. 2015 Oct 1;288(1):114-20. doi: 10.1016/j.taap.2015.07.023. Epub 2015 Jul 23. [Article]

Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:42