DICUMAROL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H12O6
Molecular Weight	336.295
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C(CC2=C(O)C3=C(OC2=O)C=CC=C3)C(=O)OC4=C1C=CC=C4

InChI

InChIKey=DOBMPNYZJYQDGZ-UHFFFAOYSA-N

InChI=1S/C19H12O6/c20-16-10-5-1-3-7-14(10)24-18(22)12(16)9-13-17(21)11-6-2-4-8-15(11)25-19(13)23/h1-8,20-21H,9H2

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB00266
Curator's Comment: https://www.ncbi.nlm.nih.gov/mesh/68001728

Dicumarol is an coumarin-like compound found in sweet clover. It is used as oral anticoagulant and acts by inhibiting the hepatic synthesis of vitamin K-dependent coagulation factors (prothrombin and factors VII, IX, and X). It results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. Dicumarol is also used in biochemical experiments as an inhibitor of reductases.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vitamin k epoxide reductase complex subunit 1 isoform 1 22 Target ID: CHEMBL1930 Sources: https://www.drugbank.ca/drugs/DB00266	Inhibitor 8504		2.0 µM [IC50]
Quinone reductase 1) 2 Target ID: CHEMBL3623 Sources: https://www.drugbank.ca/drugs/DB00266	Inhibitor 8504		10.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Blood clotting 6 Sources: https://www.drugbank.ca/drugs/DB00266	Preventing		Approved 8583	DICUMAROL Approved Use For decreasing blood clotting. Often used along with heparin for treatment of deep vein thrombosis. Launch Date 1944

C_max

Value	Dose	Co-administered	Analyte	Population
20 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/54415/	6 mg/kg single, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		DICUMAROL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
521 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/54415/	6 mg/kg single, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		DICUMAROL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.84 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/54415/	6 mg/kg single, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		DICUMAROL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.03% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/54415/	6 mg/kg single, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		DICUMAROL plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED

Doses

Dose	Population	Adverse events
200 mg 1 times / day steady, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/95337/	unhealthy, 59.8+15.3 years Health Status: unhealthy Age Group: 59.8+15.3 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/95337/	Sources: https://pubmed.ncbi.nlm.nih.gov/95337/
2100 mg single, oral Overdose Dose: 2100 mg Route: oral Route: single Dose: 2100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18920084	unknown Health Status: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/18920084	Disc. AE: Distended blood vessels... AEs leading to discontinuation/dose reduction: Distended blood vessels (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/18920084

AEs

AE	Significance	Dose	Population
Distended blood vessels	1 patient Disc. AE	2100 mg single, oral Overdose Dose: 2100 mg Route: oral Route: single Dose: 2100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18920084	unknown Health Status: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/18920084

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT 45

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
UGT 70	inhibitor 4027 Sources: https://www.sciencedirect.com/science/article/pii/S0022030210004923 Page: 4.0	yes

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-016130	http://www.3bsc.com/index/pro_info.php?id=38652
AA Blocks	AA003PB9	http://www.aablocks.com/goods/Goods/detail?id=AA003PB9
Aaron Chemicals	AR003Q31	http://www.aaronchem.com/66-76-2
abcr GmbH	AB355728	http://www.abcr.com/shop/en/AB355728
Acros Organics	AC204120050	https://www.fishersci.com/shop/products/dicumarol-99-acros-organics/AC204120050
Acros Organics	AC204120250	https://www.fishersci.com/shop/products/dicumarol-99-acros-organics/AC204120250
Adooq BioScience	A14241	https://www.adooq.com/dicoumarol.html
AK Scientific, Inc. (AKSCI)	Y1603	http://www.aksci.com/item_detail.php?cat=Y1603
Alfa Chemistry	AP66762	https://reagents.alfa-chemistry.com/product/dicoumarol-cas-66-76-2-cas-66-76-2-14835.html
Ambinter	Amb1156174	http://www.ambinter.com/reference/1156174
Ambinter	Amb19517277	http://www.ambinter.com/reference/19517277
Angel Pharmatech	AG200407	http://www.angelpharmatech.com/66-76-2.html
Angene	AGN-PC-0AAENX	http://www.angenechemical.com/productshow/AGN-PC-0AAENX.html
Aurora Fine Chemicals LLC	K00.217.222	http://online.aurorafinechemicals.com/info?ID=K00.217.222
Aurum Pharmatech LLC	H2893	http://www.Aurumpharmatech.com/Product/ProductDetails/H2893
BioCrick	BCC9225	http://www.biocrick.com/Dicoumarol-BCC9225.html
BioSynth	W-203471	https://www.biosynth.com/en/products/life-science/dyes-stains-indicators-labels/products/W-203471.html
Calbiochem	287897	http://www.emdbiosciences.com/product/287897
Chem Scene	CS-7962	http://www.chemscene.com/66-76-2.html
Chemenu	CM110352	http://www.chemenu.com/products/CM110352
Chemspace	CSSB00000695618	https://chem-space.com/CSSB00000695618
DC Chemicals	DC31650	http://www.dcchemicals.com//product_show-Dicumarol.html
EMD Millipore	287897	http://www.emdbiosciences.com/product/287897
Enamine	Z57170530	https://www.enaminestore.com/catalog/Z57170530
eNovation Chemicals	D134743	https://www.enovationchem.com/ProductDetails.asp?ProductID=D134743
eNovation Chemicals	D673955	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673955
Finetech	FT-0624734	http://www.finetechnology-ind.com/prod/detail/pub/66-76-2.html
Glentham Life Sciences	GL3972	http://www.glentham.com/products/product/GL3972/
iChemical	EBD211567	http://www.ichemical.com/products/66-76-2.html
LGC Standards	DRE-C12581000	https://www.lgcstandards.com/US/en/p/DRE-C12581000
LGC Standards	LGCFOR3051.00	https://www.lgcstandards.com/US/en/p/LGCFOR3051.00
LGC Standards	MM3051.00	https://www.lgcstandards.com/US/en/p/MM3051.00
mcule	MCULE-8095183287	https://mcule.com/MCULE-8095183287/
MedChem Express	HY-N0645	https://www.medchemexpress.com/Dicoumarol.html
Sigma-Aldrich	1190008_USP	http://www.sigmaaldrich.com/catalog/product/usp/1190008?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	218936_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/218936?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	M1390_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/m1390?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S014354	http://www.sinfoobiotech.com/product/1017752
Smolecule	S525977	http://www.smolecule.com/products/s525977
TCI (Tokyo Chemical Industry)	M0216	http://www.tcichemicals.com/eshop/en/us/commodity/M0216/index.html
THE BioTek	bt-264461	https://www.thebiotek.com/product/inhibitors/bt-264461
Vesino Industrial Co Ltd	VZ31493	http://www.vsnchem.com/goto/product/43043/

PubMed

Title	Date	PubMed
NAD(P)H:quinone oxidoreductase 1 (NQO1) competes with 20S proteasome for binding with C/EBPα leading to its stabilization and protection against radiation-induced myeloproliferative disease.	2012-12-07	23086932
Stress-induced NQO1 controls stability of C/EBPα against 20S proteasomal degradation to regulate p63 expression with implications in protection against chemical-induced skin cancer.	2012-10-04	22249251
NAD(P)H:quinone oxidoreductase 1 is induced by progesterone in cardiomyocytes.	2012-06	21947872
Discovery of 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]thiophene-2-carboxylic acid derivatives as G protein-coupled receptor 35 (GPR35) agonists.	2011-10-27	21950657
Cross talk between keratinocytes and dendritic cells: impact on the prediction of sensitization.	2011-10	21742781
Inhibition of renal NQO1 activity by dicoumarol suppresses nitroreduction of aristolochic acid I and attenuates its nephrotoxicity.	2011-08	21613233
Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.	2011-06	21427056
Cost-effective interrogation of single nucleotide polymorphisms using the mismatch amplification mutation assay and capillary electrophoresis.	2010-12	21064143
Protective effect of sulforaphane against cisplatin-induced mitochondrial alterations and impairment in the activity of NAD(P)H: quinone oxidoreductase 1 and γ glutamyl cysteine ligase: studies in mitochondria isolated from rat kidney and in LLC-PK1 cells.	2010-11-10	20732396
Biochemical mechanism of caffeic acid phenylethyl ester (CAPE) selective toxicity towards melanoma cell lines.	2010-10-06	20685355
Mechanisms of the different DNA adduct forming potentials of the urban air pollutants 2-nitrobenzanthrone and carcinogenic 3-nitrobenzanthrone.	2010-07-19	20545351
Finding new enzymes from bacterial physiology: a successful approach illustrated by the detection of novel oxidases in Marinomonas mediterranea.	2010-03-05	20411113
Analysis of couch position tolerance limits to detect mistakes in patient setup.	2009-10-29	19918218
Low levels of the air pollutant 1-nitropyrene induce DNA damage, increased levels of reactive oxygen species and endoplasmic reticulum stress in human endothelial cells.	2009-07-28	19460413
The role of aryl hydrocarbon receptor in regulation of enzymes involved in metabolic activation of polycyclic aromatic hydrocarbons in a model of rat liver progenitor cells.	2009-07-15	19497421
NAD(P)H quinone oxidoreductase 1 is essential for ozone-induced oxidative stress in mice and humans.	2009-07	19059883
The catecholaminergic RCSN-3 cell line: a model to study dopamine metabolism.	2008-06-05	18522901
Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro.	2008-02-01	17959154
Capsaicin induces heme oxygenase-1 expression in HepG2 cells via activation of PI3K-Nrf2 signaling: NAD(P)H:quinone oxidoreductase as a potential target.	2007-12	17979524
Role of NAD(P)H:quinone oxidoreductase 1 on tumor necrosis factor-alpha-induced migration of human vascular smooth muscle cells.	2007-11-01	17669387
Mitochondrial production of reactive oxygen species mediate dicumarol-induced cytotoxicity in cancer cells.	2006-12-08	17040906
[Proteus penneri].	2006-10	17125662
Arsenite pretreatment enhances the cytotoxicity of mitomycin C in human cancer cell lines via increased NAD(P)H quinone oxidoreductase 1 expression.	2006-08-01	16494910
Molecular cloning of a novel type of rat cytoplasmic 17beta-hydroxysteroid dehydrogenase distinct from the type 5 isozyme.	2006-06	16788056
Mechanism of cell cycle regulation by FIP200 in human breast cancer cells.	2005-08-01	16061648
Dicoumarol relieves serum withdrawal-induced G0/1 blockade in HL-60 cells through a superoxide-dependent mechanism.	2005-06-01	15896341
Enzymatic properties of a member (AKR1C19) of the aldo-keto reductase family.	2005-06	15930748
Environmental pollutant and potent mutagen 3-nitrobenzanthrone forms DNA adducts after reduction by NAD(P)H:quinone oxidoreductase and conjugation by acetyltransferases and sulfotransferases in human hepatic cytosols.	2005-04-01	15805261
Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication.	2005-02-15	15639223
Enhanced cytotoxicity of bioreductive antitumor agents with dimethyl fumarate in human glioblastoma cells.	2005-02	15655414
Chromium (VI)-induced cytotoxicity to osteoblast-derived cells.	1999-12	20654563
Fulminant hepatic failure associated with dicoumarol therapy.	1998-02	9548270
The role of NAD(P)H:quinone oxidoreductase in quinone-mediated p21 induction in human colon carcinoma cells.	1997-10-15	9343371
Roles of DT diaphorase in the genotoxicity of nitroaromatic compounds in human and fish cell lines.	1997-10-10	9310146
Coumarin-based inhibitors of HIV integrase.	1997-01-17	9003523
Inhibition kinetics of camel lens zeta-crystallin: multiple inhibition studies.	1996-08	9204392
Antiretroviral agents as inhibitors of both human immunodeficiency virus type 1 integrase and protease.	1996-06-21	8691444
Discovery of novel, non-peptide HIV-1 protease inhibitors by pharmacophore searching.	1996-05-10	8642563
Molecular mechanisms of tirapazamine (SR 4233, Win 59075)-induced hepatocyte toxicity under low oxygen concentrations.	1995-04	7710944
Aspirin-like drugs can protect human T lymphocytes against benzoquinone cytotoxicity: evidence for a NAD(P)H:quinone reductase-dependent mechanism.	1995	8572925
Dicoumarol and warfarin.	1991-08	18610395
Metabolism of mitomycin C by DT-diaphorase: role in mitomycin C-induced DNA damage and cytotoxicity in human colon carcinoma cells.	1990-12-01	1701346
Activation and deactivation of quinones catalyzed by DT-diaphorase. Evidence for bioreductive activation of diaziquone (AZQ) in human tumor cells and detoxification of benzene metabolites in bone marrow stroma.	1990	2113030
Spontaneous anticoagulant-induced hemopericardium with tamponade.	1982	6184935
Comparison of graphical and computerized methods for calculating binding parameters for two strongly bound drugs to human serum albumin.	1976-08	62049
Pineal apoplexy associated with anticoagulant therapy. Case report.	1976-08	59801
Management of thrombo-embolism after aortic valve replacement with the Björk-Shiley tilting disc valve. Medicamental prevention with dicumarol in comparison with dipyridamole - acetylsalicylic acid. Surgical treatment of prosthetic thrombosis.	1975	54935
Intraocular hemorrhage and blindness associated with systemic anticoagulation.	1972-06-05	4112318
Unusual gastrointestinal reaction to bishydroxycoumarin(Dicumarol).	1968-07	4173338
Urinary tract complications of anticoagulation therapy; "pseudotumour" of the kidney.	1968-03	4171018

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Oral

In Vitro Use Guide

Dicoumarol inhibits rat liver microsomal vitamin K epoxide reductase with IC50=2 uM and cytosolic DT-diaphorase with IC50=0.05 uM.

Name

Type

Language

DICOUMAROL

Preferred Name

English

DICUMAROL

Official Name

English

dicoumarol [INN]

Common Name

English

3,3'-METHYLENEBIS(4-HYDROXYCOUMARIN)

Systematic Name

English

DICUMAROL [ORANGE BOOK]

Common Name

English

DICOUMAROLUM [WHO-IP LATIN]

Common Name

English

DICOUMAROL [WHO-IP]

Common Name

English

DICOUMAROL [MART.]

Common Name

English

DICUMAROL [USAN]

Common Name

English

DICUMAROL [HSDB]

Common Name

English

NSC-221570

Code

English

DICUMAROL [MI]

Common Name

English

2H-1-BENZOPYRAN-2-ONE), 3,3'-METHYLENEBIS(4-HYDROXY-

Systematic Name

English

NSC-17860

Code

English

DICUMAROL [VANDF]

Common Name

English

Dicoumarol [WHO-DD]

Common Name

English

NSC-41834

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C45597