BRENDA - Enzyme Database

Dabigatran and dabigatran ethyl ester: potent inhibitors of ribosyldihydronicotinamide dehydrogenase (NQO2)

Michaelis, S.; Marais, A.; Schrey, A.K.; Graebner, O.Y.; Schaudt, C.; Sefkow, M.; Kroll, F.; Dreger, M.; Glinski, M.; Koester, H.; Metternich, R.; Fischer, J.J.; J. Med. Chem. 55, 3934-3944 (2012)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
1.10.5.1
dabigatran
; specific binding to the enzyme, protein interaction analysis, overview
Homo sapiens
1.10.5.1
dabigatran ethyl ester
-
Homo sapiens
1.10.5.1
ethyl 3-(2-((4-(N-(4-(tert-butoxycarbonylamino)butyl)-carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate
-
Homo sapiens
1.10.5.1
ethyl N-[(2-{[(4-carbamimidoylphenyl)amino]methyl}-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-b-alaninate
-
Homo sapiens
1.10.5.1
imatinib
-
Homo sapiens
1.10.5.1
melagatran
-
Homo sapiens
1.10.5.1
methyl 2-((S)-1-cyclohexyl-2-((R)-2-(4-(4-(4-nitrophenylsulfonamido)butylcarbamoyl)benzylcarbamoyl)-azetidin-1-yl)-2-oxoethylamino)acetate
-
Homo sapiens
1.10.5.1
methyl N-{(1R)-1-cyclohexyl-2-oxo-2-[(2S)-2-{[4-({4-[(N-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-alpha-asparaginyl)amino]butyl}carbamoyl)benzyl]carbamoyl}azetidin-1-yl]ethyl}glycinate
-
Homo sapiens
1.10.5.1
additional information
molecular dockings predicts and biological experiments confirm that dabigatran ethyl ester inhibits NQO2 even more effectively than the parent compound itself, usage of capture compounds, overview
Homo sapiens
1.10.5.1
N-{(1R)-1-cyclohexyl-2-oxo-2-[(2S)-2-{[4-({4-[(N-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-alpha-asparaginyl)amino]butyl}carbamoyl)benzyl]carbamoyl}azetidin-1-yl]ethyl}glycine
-
Homo sapiens
1.10.5.1
N-{[1-methyl-2-({[4-(N-{3-[(N-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-alpha-asparaginyl)amino]propyl}carbamimidoyl)phenyl]amino}methyl)-1H-benzimidazol-5-yl]carbonyl}-N-pyridin-2-yl-beta-alanine
-
Homo sapiens
1.10.5.1
N4-[2-(4-{4-[(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)carbamoyl]benzyl}piperazin-1-yl)ethyl]-N1-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-aspartamide
-
Homo sapiens
1.10.5.1
N4-[3-({N-[(2-{[(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-phenyl-b-alanyl}amino)propyl]-N1-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-aspartamide
-
Homo sapiens
1.10.5.1
N4-[4-({N-[(1R)-2-{(2R)-2-[(4-carbamimidoylbenzyl)carbamoyl]cyclobutyl}-1-cyclohexylprop-2-en-1-yl]glycyl}amino)butyl]-N1-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-aspartamide
-
Homo sapiens
1.10.5.1
resveratrol
-
Homo sapiens
1.10.5.1
tert-butyl 4-(4-(4-nitrophenylsulfonamido)butylcarbamoyl)-benzylcarbamate
-
Homo sapiens
1.10.5.1
tert-butyl(S)-1-cyclohexyl -2-((R)-2-(4-(4-(4-nitrophenylsulfonamido)butylcarbamoyl)benzylcarbamoyl)-azetidin-1-yl)-2-oxoethylcarbamate
-
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.10.5.1
1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone
Homo sapiens
-
1-(beta-D-ribofuranosyl)nicotinamide + a hydroquinone
-
-
?
1.10.5.1
1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + menadione
Homo sapiens
-
1-(beta-D-ribofuranosyl)nicotinamide + menadiol
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
1.10.5.1
Homo sapiens
-
-
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
1.10.5.1
Hep-G2 cell
-
Homo sapiens
-
1.10.5.1
K-562 cell
-
Homo sapiens
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.10.5.1
1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone
-
725669
Homo sapiens
1-(beta-D-ribofuranosyl)nicotinamide + a hydroquinone
-
-
-
?
1.10.5.1
1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + menadione
-
725669
Homo sapiens
1-(beta-D-ribofuranosyl)nicotinamide + menadiol
-
-
-
?
Cofactor
EC Number
Cofactor
Commentary
Organism
Structure
1.10.5.1
FAD
-
Homo sapiens
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
1.10.5.1
additional information
-
additional information
Michaelis-Menten inhibition kinetics
Homo sapiens
1.10.5.1
0.0009
-
dabigatran ethyl ester
pH and temperature not specified in the publication
Homo sapiens
1.10.5.1
0.07
-
dabigatran
pH and temperature not specified in the publication
Homo sapiens
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
1.10.5.1
0.0008
-
pH and temperature not specified in the publication
Homo sapiens
dabigatran ethyl ester
1.10.5.1
0.06
-
pH and temperature not specified in the publication
Homo sapiens
dabigatran
Cofactor (protein specific)
EC Number
Cofactor
Commentary
Organism
Structure
1.10.5.1
FAD
-
Homo sapiens
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
1.10.5.1
0.0008
-
pH and temperature not specified in the publication
Homo sapiens
dabigatran ethyl ester
1.10.5.1
0.06
-
pH and temperature not specified in the publication
Homo sapiens
dabigatran
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
1.10.5.1
dabigatran
; specific binding to the enzyme, protein interaction analysis, overview
Homo sapiens
1.10.5.1
dabigatran ethyl ester
-
Homo sapiens
1.10.5.1
ethyl 3-(2-((4-(N-(4-(tert-butoxycarbonylamino)butyl)-carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate
-
Homo sapiens
1.10.5.1
ethyl N-[(2-{[(4-carbamimidoylphenyl)amino]methyl}-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-b-alaninate
-
Homo sapiens
1.10.5.1
imatinib
-
Homo sapiens
1.10.5.1
melagatran
-
Homo sapiens
1.10.5.1
methyl 2-((S)-1-cyclohexyl-2-((R)-2-(4-(4-(4-nitrophenylsulfonamido)butylcarbamoyl)benzylcarbamoyl)-azetidin-1-yl)-2-oxoethylamino)acetate
-
Homo sapiens
1.10.5.1
methyl N-{(1R)-1-cyclohexyl-2-oxo-2-[(2S)-2-{[4-({4-[(N-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-alpha-asparaginyl)amino]butyl}carbamoyl)benzyl]carbamoyl}azetidin-1-yl]ethyl}glycinate
-
Homo sapiens
1.10.5.1
additional information
molecular dockings predicts and biological experiments confirm that dabigatran ethyl ester inhibits NQO2 even more effectively than the parent compound itself, usage of capture compounds, overview
Homo sapiens
1.10.5.1
N-{(1R)-1-cyclohexyl-2-oxo-2-[(2S)-2-{[4-({4-[(N-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-alpha-asparaginyl)amino]butyl}carbamoyl)benzyl]carbamoyl}azetidin-1-yl]ethyl}glycine
-
Homo sapiens
1.10.5.1
N-{[1-methyl-2-({[4-(N-{3-[(N-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-alpha-asparaginyl)amino]propyl}carbamimidoyl)phenyl]amino}methyl)-1H-benzimidazol-5-yl]carbonyl}-N-pyridin-2-yl-beta-alanine
-
Homo sapiens
1.10.5.1
N4-[2-(4-{4-[(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)carbamoyl]benzyl}piperazin-1-yl)ethyl]-N1-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-aspartamide
-
Homo sapiens
1.10.5.1
N4-[3-({N-[(2-{[(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-phenyl-b-alanyl}amino)propyl]-N1-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-aspartamide
-
Homo sapiens
1.10.5.1
N4-[4-({N-[(1R)-2-{(2R)-2-[(4-carbamimidoylbenzyl)carbamoyl]cyclobutyl}-1-cyclohexylprop-2-en-1-yl]glycyl}amino)butyl]-N1-{17-oxo-21-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,8,12-trioxa-16-azahenicos-1-yl}-N2-{4-[3-(trifluoromethyl)-3H-diaziren-3-yl]benzoyl}-L-aspartamide
-
Homo sapiens
1.10.5.1
resveratrol
-
Homo sapiens
1.10.5.1
tert-butyl 4-(4-(4-nitrophenylsulfonamido)butylcarbamoyl)-benzylcarbamate
-
Homo sapiens
1.10.5.1
tert-butyl(S)-1-cyclohexyl -2-((R)-2-(4-(4-(4-nitrophenylsulfonamido)butylcarbamoyl)benzylcarbamoyl)-azetidin-1-yl)-2-oxoethylcarbamate
-
Homo sapiens
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
1.10.5.1
additional information
-
additional information
Michaelis-Menten inhibition kinetics
Homo sapiens
1.10.5.1
0.0009
-
dabigatran ethyl ester
pH and temperature not specified in the publication
Homo sapiens
1.10.5.1
0.07
-
dabigatran
pH and temperature not specified in the publication
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.10.5.1
1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone
Homo sapiens
-
1-(beta-D-ribofuranosyl)nicotinamide + a hydroquinone
-
-
?
1.10.5.1
1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + menadione
Homo sapiens
-
1-(beta-D-ribofuranosyl)nicotinamide + menadiol
-
-
?
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
1.10.5.1
Hep-G2 cell
-
Homo sapiens
-
1.10.5.1
K-562 cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.10.5.1
1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone
-
725669
Homo sapiens
1-(beta-D-ribofuranosyl)nicotinamide + a hydroquinone
-
-
-
?
1.10.5.1
1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + menadione
-
725669
Homo sapiens
1-(beta-D-ribofuranosyl)nicotinamide + menadiol
-
-
-
?
General Information
EC Number
General Information
Commentary
Organism
1.10.5.1
physiological function
ribosyldihydronicotinamide dehydrogenase is a detoxification oxidoreductase, it is a flavoprotein that catalyzes the 2-electron reduction of various quinones, redox dyes, and the vitamin K menadione. NQO2 predominantly uses dihydronicotinamide riboside as the electron donor
Homo sapiens
General Information (protein specific)
EC Number
General Information
Commentary
Organism
1.10.5.1
physiological function
ribosyldihydronicotinamide dehydrogenase is a detoxification oxidoreductase, it is a flavoprotein that catalyzes the 2-electron reduction of various quinones, redox dyes, and the vitamin K menadione. NQO2 predominantly uses dihydronicotinamide riboside as the electron donor
Homo sapiens