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 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
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
Fulminant hepatic failure associated with dicoumarol therapy.	1998 Feb	9548270
NRH:quinone oxidoreductase2 (NQO2).	2000 Dec 1	11154737
Coumarin derivatives and breast-feeding.	2000 Jun	10831996
Phosphorylation is involved in the activation of metal-regulatory transcription factor 1 in response to metal ions.	2001 Nov 9	11551972
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
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
Dicoumarol relieves serum withdrawal-induced G0/1 blockade in HL-60 cells through a superoxide-dependent mechanism.	2005 Jun 1	15896341
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
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
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
Analysis of couch position tolerance limits to detect mistakes in patient setup.	2009 Oct 29	19918218
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 Nov 10	20732396
Biochemical mechanism of caffeic acid phenylethyl ester (CAPE) selective toxicity towards melanoma cell lines.	2010 Oct 6	20685355
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 is induced by progesterone in cardiomyocytes.	2012 Jun	21947872

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 GMT 2023` Edited by `admin` on `Fri Dec 15 15:06:24 GMT 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