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Details

Stereochemistry ACHIRAL
Molecular Formula C11H12O8P2
Molecular Weight 334.1557
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MENADIOL DIPHOSPHATE

SMILES

CC1=C(OP(O)(O)=O)C2=C(C=CC=C2)C(OP(O)(O)=O)=C1

InChI

InChIKey=JTNHOVZOOVVGHI-UHFFFAOYSA-N
InChI=1S/C11H12O8P2/c1-7-6-10(18-20(12,13)14)8-4-2-3-5-9(8)11(7)19-21(15,16)17/h2-6H,1H3,(H2,12,13,14)(H2,15,16,17)

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including: http://www.ncbi.nlm.nih.gov/pubmed/4859370

Menadiol diphosphate is given as a vitamin K supplement to prevent bleeding caused by vitamin K deficiency. Vitamin K is normally obtained from the diet; for example it is found in green leafy vegetables, root vegetables, cereals and dairy products. Although it cannot be made by the human body itself, a certain amount of vitamin K is also made by bacteria that live in the gut. The body normally produces bile to help it absorb fats from the gut. In conditions where there is a problem with the production of bile, for example in certain liver diseases, or if there is a blockage of the bile duct, there can be problems absorbing fats. This can lead to vitamin K deficiency, decreased production of clotting factors and an increased risk of bleeding. In these situations, menadiol diphosphate is given as a vitamin K supplement to increase the production of clotting factors. It is water soluble so is readily absorbed from the gut. Also in 1974 was made attempt to develop tritiated derivatives of Synkavit (menadiol sodium diphosphate, MNDP) of high specific activity as a radioactive drug. Among the 203 evaluable treated cases, some form of response was observed in 23 out of 151 (15·2%) receiving the drug by intravenous injections and 13 out of 52 (25%) after intra-arterial injections. For the sites and types of malignant diseases which showed responses after either intravenous or intra-arterial administration among the 55 patients surviving at least 3 months after the first injection, some form of response was observed in 32 but only 5 of these showed either a "complete" or a "partial" response.It is concluded that further investigation is desirable. Kappadione is a Vitamin K derivative, was discontinued. It was manufactured by Eli Lilly and others Company.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
Unknown

Approved Use

Unknown
Preventive
Kappadione

Approved Use

Unknown

Launch Date

1981
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.102 μg/mL
75 mg single, intravenous
dose: 75 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MENADIOL plasma
Oryctolagus cuniculus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
32.453 μg × min/mL
75 mg single, intravenous
dose: 75 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MENADIOL plasma
Oryctolagus cuniculus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
27.17 min
75 mg single, intravenous
dose: 75 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
MENADIOL plasma
Oryctolagus cuniculus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
20 mg 1 times / day multiple, oral
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 67.5
Health Status: unhealthy
Age Group: 67.5
Sex: M+F
Sources:
1360 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1360 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1360 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
DLT: Anemia, Leukopenia...
Dose limiting toxicities:
Anemia (grade 1, 5 patients)
Leukopenia (grade 1, 1 patient)
Nausea (grade 1, 2 patients)
Vomiting (grade 2, 3 patients)
Hypersensitivity reaction (grade 1, 2 patients)
Hypersensitivity reaction (grade 2, 7 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Leukopenia grade 1, 1 patient
DLT
1360 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1360 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1360 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Hypersensitivity reaction grade 1, 2 patients
DLT
1360 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1360 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1360 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Nausea grade 1, 2 patients
DLT
1360 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1360 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1360 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Anemia grade 1, 5 patients
DLT
1360 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1360 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1360 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Vomiting grade 2, 3 patients
DLT
1360 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1360 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1360 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Hypersensitivity reaction grade 2, 7 patients
DLT
1360 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 1360 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1360 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
PubMed

PubMed

TitleDatePubMed
Proteogenomic and functional analysis of chromate reduction in Acidiphilium cryptum JF-5, an Fe(III)-respiring acidophile.
2010-12
Measurement of menadione in urine by HPLC.
2010-09-15
The alternative complex III of Rhodothermus marinus and its structural and functional association with caa3 oxygen reductase.
2010-08
Cooperation of NAD(P)H:quinone oxidoreductase 1 and UDP-glucuronosyltransferases reduces menadione cytotoxicity in HEK293 cells.
2010-04-09
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2).
2009-02-24
UDP-glucuronosyltransferases 1A6 and 1A10 catalyze reduced menadione glucuronidation.
2008-06-27
2,5-dihydroxybenzyl and (1,4-dihydroxy-2-naphthyl)methyl, novel reductively armed photocages for the hydroxyl moiety.
2007-11-23
A novel chimera: the "truncated hemoglobin-antibiotic monooxygenase" from Streptomyces avermitilis.
2007-08-15
Characterization of the Desulfovibrio desulfuricans ATCC 27774 DsrMKJOP complex--a membrane-bound redox complex involved in the sulfate respiratory pathway.
2006-01-10
Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy.
2005-06
An unbiased cell morphology-based screen for new, biologically active small molecules.
2005-05
Structural and biochemical evidence for an enzymatic quinone redox cycle in Escherichia coli: identification of a novel quinol monooxygenase.
2005-03-04
Evidence for two different electron transfer pathways in the same enzyme, nitrate reductase A from Escherichia coli.
2004-06
Menadione kills trophozoites and cysts of Giardia intestinalis.
2004-05
NapGH components of the periplasmic nitrate reductase of Escherichia coli K-12: location, topology and physiological roles in quinol oxidation and redox balancing.
2004-04-01
Role of NAD(P)H:quinone oxidoreductase encoded by drgA gene in reduction of exogenous quinones in cyanobacterium Synechocystis sp. PCC 6803 cells.
2004-02
Effects of site-directed mutations on heme reduction in Escherichia coli nitrate reductase A by menaquinol: a stopped-flow study.
2003-12-09
Elimination of the disulfide bridge in the Rieske iron-sulfur protein allows assembly of the [2Fe-2S] cluster into the Rieske protein but damages the ubiquinol oxidation site in the cytochrome bc1 complex.
2003-11-25
A novel membrane-bound respiratory complex from Desulfovibrio desulfuricans ATCC 27774.
2003-08-18
Transient kinetic studies of heme reduction in Escherichia coli nitrate reductase A (NarGHI) by menaquinol.
2003-05-13
Oxygen control of nif gene expression in Klebsiella pneumoniae depends on NifL reduction at the cytoplasmic membrane by electrons derived from the reduced quinone pool.
2003-04
Roles of NapF, NapG and NapH, subunits of the Escherichia coli periplasmic nitrate reductase, in ubiquinol oxidation.
2002-04
Concerted action of DT-diaphorase and superoxide dismutase in preventing redox cycling of naphthoquinones: an evaluation.
2001-08
Redox changes of cytochrome b(559) in the presence of plastoquinones.
2001-01-05
Investigations of tritiated menadiol sodium diphosphate (T-MNDP) as a radioactive drug.
1974-05
Patents

Sample Use Guides

20 mg o.d. for 3 days of oral menadiol
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: The effect of menadiol (vitamin K3) on fresh specimens of human lymphatic neoplasms (HLN) was tested by means of the differential staining cytotoxicity assay. By itself, menadiol was moderately toxic to HLN, but not to normal lymphocytes or non-small cell lung cancer. Menadiol increased the cytotoxic effects of a number of standard agents in HLN.
2.0 ug/ml; 4.7 uM
Name Type Language
MENADIOL DIPHOSPHATE
Common Name English
1,4-NAPHTHALENEDIOL, 2-METHYL-, 1,4-BIS(DIHYDROGEN PHOSPHATE)
Preferred Name English
2-METHYL-1,4-NAPHTHALENEDIOL DIPHOSPHATE
Systematic Name English
1,4-NAPHTHALENEDIOL, 2-METHYL-, DIPHOSPHATE
Systematic Name English
1,4-NAPHTHALENEDIOL, 2-METHYL-, BIS(DIHYDROGEN PHOSPHATE)
Common Name English
MENADIOL BIS(DIHYDROGEN PHOSPHATE)
Common Name English
MENADIOL PHOSPHATE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C943
Created by admin on Mon Mar 31 18:23:18 GMT 2025 , Edited by admin on Mon Mar 31 18:23:18 GMT 2025
Code System Code Type Description
CAS
84-98-0
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PRIMARY
EPA CompTox
DTXSID10861785
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PRIMARY
PUBCHEM
8556
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PRIMARY
MESH
C023885
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PRIMARY
RXCUI
360777
Created by admin on Mon Mar 31 18:23:18 GMT 2025 , Edited by admin on Mon Mar 31 18:23:18 GMT 2025
PRIMARY RxNorm
NCI_THESAURUS
C80887
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PRIMARY
EVMPD
SUB194848
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PRIMARY
SMS_ID
100000181285
Created by admin on Mon Mar 31 18:23:18 GMT 2025 , Edited by admin on Mon Mar 31 18:23:18 GMT 2025
PRIMARY
DRUG BANK
DB14650
Created by admin on Mon Mar 31 18:23:18 GMT 2025 , Edited by admin on Mon Mar 31 18:23:18 GMT 2025
PRIMARY
FDA UNII
GRL65FEU3T
Created by admin on Mon Mar 31 18:23:18 GMT 2025 , Edited by admin on Mon Mar 31 18:23:18 GMT 2025
PRIMARY