MENADIOL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H10O2
Molecular Weight	174.1959
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC(O)=C2C=CC=CC2=C1O

InChI

InChIKey=ZJTLZYDQJHKRMQ-UHFFFAOYSA-N

InChI=1S/C11H10O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6,12-13H,1H3

HIDE SMILES / InChI

Description
Sources: http://www.netdoctor.co.uk/medicines/liver-kidney-and-urinary-system/a7076/menadiol-diphosphate/http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2036.2000.00880.x/epdf
Curator's Comment: description was created based on several sources, including: http://www.ncbi.nlm.nih.gov/pubmed/3581100

Menadiol is one of the forms of vitamin K4. Chemically, it is closely related to menadione. Oral menadiol appears to be an effectiv ealternative to intravenous phytomenadione in the correction of coagulopathies associated with obstructiveliver disease. This simplifies the care of patients with deranged clotting times requiring cholangeopancrea-tography, particularly those to be managed as out-patients. Menadiol should receive clinical testing as a chemosensitizing agent in human lymphatic neoplasms (HLN). This effect occurred at a concentration (2.0 micrograms/ml; 4.7 microM) of menadiol which is probably clinically achievable and which did not deplete intracellular glutathione.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
regulation of blood coagulation 4 Target ID: GO:0030193 Sources: http://www.netdoctor.co.uk/medicines/liver-kidney-and-urinary-system/a7076/menadiol-diphosphate/	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Correction of coagulopathy associated with cholestasis 4 Sources: http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2036.2000.00880.x/epdf	Secondary		Basic research	Unknown Approved Use Unknown
Excessive bleeding 4 Sources: https://www.medicines.org.uk/emc/PIL.5230.latest.pdf	Preventive		Approved 8429	Kappadione Approved Use Unknown Launch Date 1981

C_max

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

T_1/2

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: https://pubmed.ncbi.nlm.nih.gov/11121919/	unhealthy, 67.5 n = 12 Health Status: unhealthy Condition: coagulopathies associated with cholestasis Age Group: 67.5 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/11121919/	Sources: https://pubmed.ncbi.nlm.nih.gov/11121919/
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: https://pubmed.ncbi.nlm.nih.gov/15868379/	unhealthy, adult n = 13 Health Status: unhealthy Condition: advanced malignancy Age Group: adult Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/15868379/	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: https://pubmed.ncbi.nlm.nih.gov/15868379/

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: https://pubmed.ncbi.nlm.nih.gov/15868379/	unhealthy, adult n = 13 Health Status: unhealthy Condition: advanced malignancy Age Group: adult Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/15868379/
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: https://pubmed.ncbi.nlm.nih.gov/15868379/	unhealthy, adult n = 13 Health Status: unhealthy Condition: advanced malignancy Age Group: adult Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/15868379/
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: https://pubmed.ncbi.nlm.nih.gov/15868379/	unhealthy, adult n = 13 Health Status: unhealthy Condition: advanced malignancy Age Group: adult Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/15868379/
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: https://pubmed.ncbi.nlm.nih.gov/15868379/	unhealthy, adult n = 13 Health Status: unhealthy Condition: advanced malignancy Age Group: adult Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/15868379/
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: https://pubmed.ncbi.nlm.nih.gov/15868379/	unhealthy, adult n = 13 Health Status: unhealthy Condition: advanced malignancy Age Group: adult Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/15868379/
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: https://pubmed.ncbi.nlm.nih.gov/15868379/	unhealthy, adult n = 13 Health Status: unhealthy Condition: advanced malignancy Age Group: adult Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/15868379/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6746	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6746
ChemicalBook	CB2678939	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2678939
MolPort	MolPort-006-111-404	https://www.molport.com/shop/molecule-link/MolPort-006-111-404
ZINC	ZINC000018120050	http://zinc15.docking.org/substances/ZINC000018120050
eMolecules	36553897	https://www.emolecules.com/cgi-bin/more?vid=36553897

PubMed

Title	Date	PubMed
Investigations of tritiated menadiol sodium diphosphate (T-MNDP) as a radioactive drug.	1974 May	4859370
Concerted action of DT-diaphorase and superoxide dismutase in preventing redox cycling of naphthoquinones: an evaluation.	2001 Aug	11697195
Redox changes of cytochrome b(559) in the presence of plastoquinones.	2001 Jan 5	11022032
Roles of NapF, NapG and NapH, subunits of the Escherichia coli periplasmic nitrate reductase, in ubiquinol oxidation.	2002 Apr	11967083
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 Apr	12654011
A novel membrane-bound respiratory complex from Desulfovibrio desulfuricans ATCC 27774.	2003 Aug 18	12907302
Effects of site-directed mutations on heme reduction in Escherichia coli nitrate reductase A by menaquinol: a stopped-flow study.	2003 Dec 9	14640690
Transient kinetic studies of heme reduction in Escherichia coli nitrate reductase A (NarGHI) by menaquinol.	2003 May 13	12731882
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 Nov 25	14622010
NapGH components of the periplasmic nitrate reductase of Escherichia coli K-12: location, topology and physiological roles in quinol oxidation and redox balancing.	2004 Apr 1	14674886
Role of NAD(P)H:quinone oxidoreductase encoded by drgA gene in reduction of exogenous quinones in cyanobacterium Synechocystis sp. PCC 6803 cells.	2004 Feb	15000679
Evidence for two different electron transfer pathways in the same enzyme, nitrate reductase A from Escherichia coli.	2004 Jun	15182355
Menadione kills trophozoites and cysts of Giardia intestinalis.	2004 May	15133085
Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy.	2005 Jun	15868379
Structural and biochemical evidence for an enzymatic quinone redox cycle in Escherichia coli: identification of a novel quinol monooxygenase.	2005 Mar 4	15613473
An unbiased cell morphology-based screen for new, biologically active small molecules.	2005 May	15799708
Characterization of the Desulfovibrio desulfuricans ATCC 27774 DsrMKJOP complex--a membrane-bound redox complex involved in the sulfate respiratory pathway.	2006 Jan 10	16388601
A novel chimera: the "truncated hemoglobin-antibiotic monooxygenase" from Streptomyces avermitilis.	2007 Aug 15	17574781
2,5-dihydroxybenzyl and (1,4-dihydroxy-2-naphthyl)methyl, novel reductively armed photocages for the hydroxyl moiety.	2007 Nov 23	17958445
UDP-glucuronosyltransferases 1A6 and 1A10 catalyze reduced menadione glucuronidation.	2008 Jun 27	18423374
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2).	2009 Feb 24	19236722
Cooperation of NAD(P)H:quinone oxidoreductase 1 and UDP-glucuronosyltransferases reduces menadione cytotoxicity in HEK293 cells.	2010 Apr 9	20035715
The alternative complex III of Rhodothermus marinus and its structural and functional association with caa3 oxygen reductase.	2010 Aug	20206595
Proteogenomic and functional analysis of chromate reduction in Acidiphilium cryptum JF-5, an Fe(III)-respiring acidophile.	2010 Dec	20593301
Measurement of menadione in urine by HPLC.	2010 Sep 15	20719580

Patents

Sample Use Guides

In Vivo Use Guide

Adults: Usual therapeutic dose: 10-40mg daily Children: If, on the recommendation of a physician, a children's dosage is required, it is suggested that 5-20mg daily be given. The elderly: Recommendations for use in the elderly do not differ from those for other adults.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

MENADIOL

Common Name

English

MENADIOL [MI]

Common Name

English

MENADIOL [VANDF]

Common Name

English

Menadiol [WHO-DD]

Common Name

English

2-METHYL-1,4-NAPHTHALENEDIOL

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C943