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
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)
| Molecular Formula | C11H12O8P2 |
| Molecular Weight | 334.1557 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2036.2000.00880.x/epdfhttp://www.netdoctor.co.uk/medicines/liver-kidney-and-urinary-system/a7076/menadiol-diphosphate/Curator's Comment: description was created based on several sources, including:
http://www.ncbi.nlm.nih.gov/pubmed/4859370
Sources: http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2036.2000.00880.x/epdfhttp://www.netdoctor.co.uk/medicines/liver-kidney-and-urinary-system/a7076/menadiol-diphosphate/
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
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.102 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8866040/ |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
32.453 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8866040/ |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
27.17 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8866040/ |
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
| Dose | Population | Adverse 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 |
|
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 |
DLT: Anemia, Leukopenia... Dose limiting toxicities: Anemia (grade 1, 5 patients) Sources: 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) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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 |
Sample Use Guides
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/3581100
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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:23:18 GMT 2025
by
admin
on
Mon Mar 31 18:23:18 GMT 2025
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| Record UNII |
GRL65FEU3T
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| Record Status |
Validated (UNII)
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C943
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C80887
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