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=CC=CC=C3OC2=O)C(=O)OC4=CC=CC=C14

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 8297		2.0 µM [IC50]
Quinone reductase 1) 2 Target ID: CHEMBL3623 Sources: https://www.drugbank.ca/drugs/DB00266	Inhibitor 8297		10.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Blood clotting 6 Sources: https://www.drugbank.ca/drugs/DB00266	Preventing		Approved 8429	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 n = 71 Health Status: unhealthy Age Group: 59.8+15.3 years Sex: M+F Population Size: 71 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 n = 1 Health Status: unknown Population Size: 1 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 n = 1 Health Status: unknown Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18920084

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT 35

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
UGT 59	inhibitor 3277 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
AK Scientific, Inc. (AKSCI)	Y1603	http://www.aksci.com/item_detail.php?cat=Y1603
Aaron Chemicals	AR003Q31	http://www.aaronchem.com/66-76-2
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
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
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/
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
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/
abcr GmbH	AB355728	http://www.abcr.com/shop/en/AB355728
eNovation Chemicals	D134743	https://www.enovationchem.com/ProductDetails.asp?ProductID=D134743
eNovation Chemicals	D673955	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673955
iChemical	EBD211567	http://www.ichemical.com/products/66-76-2.html
mcule	MCULE-8095183287	https://mcule.com/MCULE-8095183287/

PubMed

Title	Date	PubMed
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
Dicoumarol and warfarin.	1991 Aug	18610395
[Fatal cerebral hemorrhage caused by overdose of dicumarol, report of a case].	1992 Feb	1374271
Identification and characterization of the enzymatic activity of zeta-crystallin from guinea pig lens. A novel NADPH:quinone oxidoreductase.	1992 Jan 5	1370456
Reduction of chromium(VI) to chromium(V) by rat liver cytosolic and microsomal fractions: is DT-diaphorase involved?	1992 Jul	1379126
Inhibition kinetics of camel lens zeta-crystallin: multiple inhibition studies.	1996 Aug	9204392
Antiretroviral agents as inhibitors of both human immunodeficiency virus type 1 integrase and protease.	1996 Jun 21	8691444
Discovery of novel, non-peptide HIV-1 protease inhibitors by pharmacophore searching.	1996 May 10	8642563
Coumarin-based inhibitors of HIV integrase.	1997 Jan 17	9003523
Copper neurotoxicity is dependent on dopamine-mediated copper uptake and one-electron reduction of aminochrome in a rat substantia nigra neuronal cell line.	2001 Apr	11299314
Transient activation of Jun N-terminal kinases and protection from apoptosis by the insulin-like growth factor I receptor can be suppressed by dicumarol.	2001 Jun 1	11278392
P53 hot-spot mutants are resistant to ubiquitin-independent degradation by increased binding to NAD(P)H:quinone oxidoreductase 1.	2003 Dec 9	14634213
Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride.	2003 Jul	12880296
Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism.	2003 Sep 1	14500388
JNK activation is a mediator of arsenic trioxide-induced apoptosis in acute promyelocytic leukemia cells.	2004 May 1	14701702
Mitochondrial production of reactive oxygen species mediate dicumarol-induced cytotoxicity in cancer cells.	2006 Dec 8	17040906
Role of NAD(P)H:quinone oxidoreductase 1 on tumor necrosis factor-alpha-induced migration of human vascular smooth muscle cells.	2007 Nov 1	17669387
The catecholaminergic RCSN-3 cell line: a model to study dopamine metabolism.	2008 May-Jun	18522901
NAD(P)H quinone oxidoreductase 1 is essential for ozone-induced oxidative stress in mice and humans.	2009 Jul	19059883
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 Jul 15	19497421
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 Jul 28	19460413
Analysis of couch position tolerance limits to detect mistakes in patient setup.	2009 Oct 29	19918218
Cost-effective interrogation of single nucleotide polymorphisms using the mismatch amplification mutation assay and capillary electrophoresis.	2010 Dec	21064143
Inhibition of renal NQO1 activity by dicoumarol suppresses nitroreduction of aristolochic acid I and attenuates its nephrotoxicity.	2011 Aug	21613233
Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.	2011 Jun	21427056
Cross talk between keratinocytes and dendritic cells: impact on the prediction of sensitization.	2011 Oct	21742781

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

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

DICOUMAROL

Official 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