Natural Product (NP) Details

General Information of the NP (ID: NP4705)
Name
Dicoumarol
Synonyms
dicumarol; dicoumarol; 66-76-2; Bishydroxycoumarin; dicoumarin; melitoxin; bis-hydroxycoumarin; Antitrombosin; Baracoumin; Dicoumal; Dicumarine; Acadyl; Acavyl; Dicuman; Dicumol; Trombosan; Dufalone; Kumoran; Temparin; Cumid; Cuma; Dicumaol R; 3,3'-Methylenebis(4-hydroxycoumarin); Bis(4-hydroxycoumarin-3-yl)methane; Dicoumarolum; Bis-3,3'-(4-hydroxycoumarinyl)methane; Di-(4-hydroxy-3-coumarinyl)methane; Di-4-hydroxy-3,3'-methylenedicoumarin; 3,3'-methylenebis(4-hydroxy-2H-chromen-2-one); 3,3'-Methylen-bis(4-hydroxy-cumarin); 3,3'-Methylenebis(4-hydroxy-2H-1-benzopyran-2-one); 3,3'-Methylene-bis(4-hydroxycoumarine); 3,3'-Methylenebis(4-hydroxy-1,2-benzopyrone); NC 034; 2H-1-Benzopyran-2-one, 3,3'-methylenebis[4-hydroxy-; 3,3'-Metilen-bis(4-idrossi-cumarina); 3,3'-Methyleen-bis(4-hydroxy-cumarine); 3,3'-methanediylbis(4-hydroxy-2H-chromen-2-one); UNII-7QID3E7BG7; C19H12O6; NSC 17860; Dicoumarol (INN); 3,3'-Methylenebis[4-hydroxycoumarin]; NSC 221570; 3,3'-Methylene-bis(4-hydroxycoumarin); Coumarin, 3,3'-methylenebis(4-hydroxy-; 4-hydroxy-3-[(4-hydroxy-2-oxochromen-3-yl)methyl]chromen-2-one; 7QID3E7BG7; CHEMBL1466; CHEBI:4513; Anathrombase; Apekumarol; Dicoumerol; Dicumarinum; Dicumarolum; 4-hydroxy-3-[(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2H-chromen-2-one; Dicoumarol [INN]; NSC17860; NSC41834; 3,2-benzopyrone]; Dicumarol, 99%; MFCD00006857; CAS-66-76-2; Dicumarolo [DCIT]; NCGC00016296-01; Dwukumarol [Polish]; Dicumarolo; Dikumarol; Dwukumarol; DSSTox_CID_1729; 3,3'-Methylenebis[4-hydroxy-1,2-benzopyrone]; DSSTox_RID_76296; Dicumarol [INN-Spanish]; DSSTox_GSID_21729; Dicoumarolum [INN-Latin]; CHEMBL43154; 3,3'-Methylenebis[4-hydroxy-2H-1-benzopyran-2-one]; 2H-1-Benzopyran-2-one, 3,3'-methylenebis(4-hydroxy-; Coumarin,3'-methylenebis[4-hydroxy-; Dicumarol (TN); Dicumarol (USAN); CCRIS 3713; Bis-3,3'-(4-oxycoumarinyl)ethylacetate; NSC221570; HSDB 3223; WLN: T66 BOVJ EQ D1- DT66 BOVJ EQ; SR-05000001605; 4,4'-Dihydroxy-3,3'-methylene bis coumarin; Dicumarol [USAN:USP]; 2H-1-Benzopyran-2-one,3'-methylenebis[4-hydroxy-; EINECS 200-632-9; NSC 41834; 2H-1-Benzopyran-2-one],3'-methylenebis[4-hydroxy-; 3,3'-Methylen-bis(4-hydroxy-cumarin) [German]; 3,3'-Methyleen-bis(4-hydroxy-cumarine) [Dutch]; 3,3'-Methylene-bis(4-hydroxycoumarine) [French]; 3,3'-Metilen-bis(4-idrossi-cumarina) [Italian]; BRN 0335444; AI3-14546; 4-hydroxy-3-((4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)-2H-chromen-2-one; symmetric dicoumarol analogue, 1; uncoupler of oxidative respiration; Prestwick_90; 2H-1-Benzopyran-2-one), 3,3'-methylenebis(4-hydroxy-; Spectrum_000165; Prestwick0_000785; Prestwick1_000785; Prestwick2_000785; Prestwick3_000785; Spectrum2_000144; Spectrum3_000387; Spectrum4_000508; Spectrum5_000871; M0216; ChemDiv2_003436; Oprea1_150990; SCHEMBL33891; SCHEMBL33892; BSPBio_000890; BSPBio_002173; CBDivE_003005; KBioGR_001055; KBioSS_000645; 5-19-06-00682 (Beilstein Handbook Reference); DivK1c_000896; SPECTRUM1500239; SPBio_000248; SPBio_002829; BPBio1_000980; GTPL6808; DTXSID8021729; BDBM35525; HMS502M18; KBio1_000896; KBio2_000645; KBio2_003213; KBio2_005781; KBio3_001393; Dicoumarol - CAS 66-76-2; NINDS_000896; HMS1378M04; HMS1570M12; HMS1920E20; HMS2091M10; HMS2097M12; HMS3652P10; HMS3714M12; HMS3744M19; HMS3865F03; Pharmakon1600-01500239; HY-N0645; ZINC3869855; Tox21_110357; 3,3'-Methylenbis(4-hydroxycumarin); BBL008904; CCG-34550; NSC-17860; NSC756733; s4299; STK801287; AKOS000520650; Tox21_110357_1; AM10016; CS-7962; DB00266; ETHYLM-TRIFLUOROMETHYLCARBANILATE; MCULE-8095183287; NSC-756733; VZ31493; IDI1_000896; NCGC00016296-02; NCGC00016296-03; NCGC00016296-04; NCGC00016296-05; NCGC00016296-07; NCGC00094650-01; NCGC00094650-02; AS-19619; SBI-0051343.P003; FT-0624734; H2893; SW196402-3; Y1603; 3,3''''''''-methylenebis[4-hydroxycoumarin; 3,3'-Methylene-bis(4-hydroxycoumarin), 99%; A14241; C00796; D03798; 3,3''''''''-methylenebis(4-hydroxy-coumarin; 3,3''''''''-methylenebis(4-hydroxycoumarin); AB00051966_05; Coumarin, 3,3'-methylenebis[4-hydroxy- (8CI); Q420886; SR-05000001605-1; SR-05000001605-3; SR-05000001605-4; W-203471; BRD-K82236179-001-05-0; BRD-K82236179-001-06-8; Z57170530; 2H-1-Benzopyran-2-one, 3,3'-methylenebis[4-hydroxy- (9CI); Dicumarol, United States Pharmacopeia (USP) Reference Standard; 4-hydroxy-3-[(4-hydroxy-2-oxo-chromen-3-yl)methyl]chromen-2-one
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Species Origin Vanilla fragrans ...     Click to Show/Hide
Vanilla fragrans
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Asparagales
Family: Orchidaceae
Genus: Vanilla
Species: Vanilla fragrans
Disease Thrombosis [ICD-11: DB61-GB90] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C19H12O6
PubChem CID
54676038
Canonical SMILES
C1=CC=C2C(=C1)C(=C(C(=O)O2)CC3=C(C4=CC=CC=C4OC3=O)O)O
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
InChIKey
DOBMPNYZJYQDGZ-UHFFFAOYSA-N
CAS Number
CAS 66-76-2
ChEBI ID
CHEBI:4513
Herb ID
HBIN023695
TTD Drug ID
D02TJS
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cisplatin      Bladder cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation p105  Molecule Info 
Pathway MAP
                    In-vitro Model Caki Clear cell renal cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Dicoumarol showed sensitizing effect of on TRAIL-mediated apoptosis.
          Gemcitabine      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression NQO1  Molecule Info 
Pathway MAP
                    In-vitro Model KKU-100 CVCL_3996 Hilar cholangiocarcinoma Homo sapiens
KKU-OCA17 CVCL_M265 Intrahepatic cholangiocarcinoma Homo sapiens
KKU-213B CVCL_M264 Cholangiocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 NQO1 may be important in sensitizing cells to anticancer drugs and inhibition of NQO1 may be a strategy for the treatment of CCA.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Oxaliplatin      Colorectal cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CYB5R2  Molecule Info 
Pathway MAP
                    In-vitro Model SNU-449 CVCL_0454 Adult hepatocellular carcinoma Homo sapiens
SNU-387 CVCL_0250 Adult hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Dicoumarol enhances gemcitabine-induced cytotoxicity in high NQO1-expressing cholangiocarcinoma cells.
          Doxorubicin      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation p38 beta  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation TP53  Molecule Info 
Pathway MAP
                    In-vitro Model RT-112 CVCL_1670 Bladder carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Concomitant use of dicoumarol could enhance the cytotoxicity of doxorubicin in urothelial cancer cells with wt-p53 through the p53/p21/p38 MAPK pathways.
Target and Pathway
Target(s) Vitamin K epoxide reductase complex 1 (VKORC1)  Molecule Info  [5]
KEGG Pathway Ubiquinone and other terpenoid-quinone biosynthesis Click to Show/Hide
Pathwhiz Pathway Vitamin K Metabolism Click to Show/Hide
2 Coagulation
WikiPathways PTM: gamma carboxylation, hypusine formation and arylsulfatase activation Click to Show/Hide
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6808).
Reference 2 Dicoumarol sensitizes renal cell carcinoma Caki cells to TRAIL-induced apoptosis through down-regulation of Bcl-2, Mcl-1 and c-FLIP in a NQO1-independent manner. Exp Cell Res. 2014 Apr 15;323(1):144-154.
Reference 3 Dicoumarol enhances gemcitabine-induced cytotoxicity in high NQO1-expressing cholangiocarcinoma cells. World J Gastroenterol. 2010 May 21;16(19):2362-70.
Reference 4 Dicoumarol enhances doxorubicin-induced cytotoxicity in p53 wild-type urothelial cancer cells through p38 activation. BJU Int. 2010 Feb;105(4):558-64.
Reference 5 Vitamin K antagonism of coumarin intoxication in the rat. Thromb Haemost. 1986 Apr 30;55(2):235-9.
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