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

Molecular Formula	C19H12O6
Molecular Weight	336.295
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 -8.0222401E11

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
Unusual gastrointestinal reaction to bishydroxycoumarin(Dicumarol).	1968 Jul	4173338
Urinary tract complications of anticoagulation therapy; "pseudotumour" of the kidney.	1968 Mar	4171018
Intraocular hemorrhage and blindness associated with systemic anticoagulation.	1972 Jun 5	4112318
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
[Fatal cerebral hemorrhage caused by overdose of dicumarol, report of a case].	1992 Feb	1374271
Reduction of chromium(VI) to chromium(V) by rat liver cytosolic and microsomal fractions: is DT-diaphorase involved?	1992 Jul	1379126
Aspirin-like drugs can protect human T lymphocytes against benzoquinone cytotoxicity: evidence for a NAD(P)H:quinone reductase-dependent mechanism.	1995	8572925
Molecular mechanisms of tirapazamine (SR 4233, Win 59075)-induced hepatocyte toxicity under low oxygen concentrations.	1995 Apr	7710944
Discovery of novel, non-peptide HIV-1 protease inhibitors by pharmacophore searching.	1996 May 10	8642563
Roles of DT diaphorase in the genotoxicity of nitroaromatic compounds in human and fish cell lines.	1997 Oct 10	9310146
The role of NAD(P)H:quinone oxidoreductase in quinone-mediated p21 induction in human colon carcinoma cells.	1997 Oct 15	9343371
Fulminant hepatic failure associated with dicoumarol therapy.	1998 Feb	9548270
Chromium (VI)-induced cytotoxicity to osteoblast-derived cells.	1999 Dec	20654563
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
Dicoumarol: a unique microtubule stabilizing natural product that is synergistic with Taxol.	2003 Mar 15	12649179
Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism.	2003 Sep 1	14500388
Geomorphological evolution and environmental reclamation of Fusaro Lagoon (Campania Province, southern Italy).	2004 Apr	14749109
Treatment of pancreatic cancer cells with dicumarol induces cytotoxicity and oxidative stress.	2004 Jul 1	15240547
JNK activation is a mediator of arsenic trioxide-induced apoptosis in acute promyelocytic leukemia cells.	2004 May 1	14701702
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 Apr 1	15805261
Enhanced cytotoxicity of bioreductive antitumor agents with dimethyl fumarate in human glioblastoma cells.	2005 Feb	15655414
Arsenite pretreatment enhances the cytotoxicity of mitomycin C in human cancer cell lines via increased NAD(P)H quinone oxidoreductase 1 expression.	2006 Aug 1	16494910
Molecular cloning of a novel type of rat cytoplasmic 17beta-hydroxysteroid dehydrogenase distinct from the type 5 isozyme.	2006 Jun	16788056
[Proteus penneri].	2006 Oct	17125662
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 Dec	17979524
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 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
Cost-effective interrogation of single nucleotide polymorphisms using the mismatch amplification mutation assay and capillary electrophoresis.	2010 Dec	21064143
Finding new enzymes from bacterial physiology: a successful approach illustrated by the detection of novel oxidases in Marinomonas mediterranea.	2010 Mar 5	20411113
Biochemical mechanism of caffeic acid phenylethyl ester (CAPE) selective toxicity towards melanoma cell lines.	2010 Oct 6	20685355
Inhibition of renal NQO1 activity by dicoumarol suppresses nitroreduction of aristolochic acid I and attenuates its nephrotoxicity.	2011 Aug	21613233
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 Oct 27	21950657
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 Dec 7	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 Oct 4	22249251

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:06:24 UTC 2023` Edited by `admin` on `Fri Dec 15 15:06:24 UTC 2023`
Record UNII	7QID3E7BG7
Record Status	`Validated (UNII)`
Record Version

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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