General Information of Target

Target ID LDTP02798
Target Name NAD(P)H dehydrogenase [quinone] 1 (NQO1)
Gene Name NQO1
Gene ID 1728
Synonyms
DIA4; NMOR1; NAD(P)H dehydrogenase [quinone] 1; EC 1.6.5.2; Azoreductase; DT-diaphorase; DTD; Menadione reductase; NAD(P)H:quinone oxidoreductase 1; Phylloquinone reductase; Quinone reductase 1; QR1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MVGRRALIVLAHSERTSFNYAMKEAAAAALKKKGWEVVESDLYAMNFNPIISRKDITGKL
KDPANFQYPAESVLAYKEGHLSPDIVAEQKKLEAADLVIFQFPLQWFGVPAILKGWFERV
FIGEFAYTYAAMYDKGPFRSKKAVLSITTGGSGSMYSLQGIHGDMNVILWPIQSGILHFC
GFQVLEPQLTYSIGHTPADARIQILEGWKKRLENIWDETPLYFAPSSLFDLNFQAGFLMK
KEVQDEEKNKKFGLSVGHHLGKSIPTDNQIKARK
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
NAD(P)H dehydrogenase (quinone) family
Subcellular location
Cytoplasm, cytosol
Function
Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons are sequentially transferred from NAD(P)H to flavin cofactor and then from reduced flavin to the quinone, bypassing the formation of semiquinone and reactive oxygen species. Regulates cellular redox state primarily through quinone detoxification. Reduces components of plasma membrane redox system such as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone forms. In the process may function as superoxide scavenger to prevent hydroquinone oxidation and facilitate excretion. Alternatively, can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential. Acts as a gatekeeper of the core 20S proteasome known to degrade proteins with unstructured regions. Upon oxidative stress, interacts with tumor suppressors TP53 and TP73 in a NADH-dependent way and inhibits their ubiquitin-independent degradation by the 20S proteasome.
TTD ID
T52389
Uniprot ID
P15559
DrugMap ID
TT8XK6L
Ensemble ID
ENST00000320623.10
HGNC ID
HGNC:2874
ChEMBL ID
CHEMBL3623

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
SW756 SNV: p.R201Q .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 16 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
TG42
 Probe Info 
89.63  LDD0326  [1]
C-Sul
 Probe Info 
5.08  LDD0066  [2]
YN-4
 Probe Info 
100.00  LDD0445  [3]
STPyne
 Probe Info 
K209(9.17)  LDD0277  [4]
AZ-9
 Probe Info 
E206(1.01); E246(0.96)  LDD2208  [5]
Probe 1
 Probe Info 
Y76(7.65)  LDD3495  [6]
HHS-482
 Probe Info 
Y129(1.28); Y68(0.90); Y76(0.96)  LDD0285  [7]
HHS-475
 Probe Info 
Y76(0.91); Y127(0.98); Y129(1.09)  LDD0264  [8]
W1
 Probe Info 
W208(1.14)  LDD0237  [9]
ATP probe
 Probe Info 
N.A.  LDD0035  [10]
Acrolein
 Probe Info 
H80(0.00); H12(0.00); H259(0.00); H258(0.00)  LDD0217  [11]
Crotonaldehyde
 Probe Info 
H12(0.00); H259(0.00)  LDD0219  [11]
Methacrolein
 Probe Info 
H80(0.00); H12(0.00)  LDD0218  [11]
TER-AC
 Probe Info 
N.A.  LDD0426  [12]
TPP-AC
 Probe Info 
N.A.  LDD0427  [12]
HHS-465
 Probe Info 
Y129(0.00); K135(0.00); Y76(0.00); K77(0.00)  LDD2240  [13]
PAL-AfBPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FFF probe11
 Probe Info 
7.73  LDD0472  [14]
FFF probe13
 Probe Info 
20.00  LDD0475  [14]
FFF probe6
 Probe Info 
13.39  LDD0468  [14]
Staurosporine capture compound
 Probe Info 
12.00  LDD0083  [15]
DA-2
 Probe Info 
N.A.  LDD0072  [16]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa H80(0.00); H12(0.00)  LDD0222  [11]
 LDCM0116  HHS-0101 DM93 Y76(0.91); Y127(0.98); Y129(1.09)  LDD0264  [8]
 LDCM0117  HHS-0201 DM93 Y76(0.82); Y129(1.04); Y127(1.29)  LDD0265  [8]
 LDCM0118  HHS-0301 DM93 Y76(0.93); Y129(1.36); Y127(1.75)  LDD0266  [8]
 LDCM0119  HHS-0401 DM93 Y129(0.91); Y127(0.96); Y76(6.13)  LDD0267  [8]
 LDCM0120  HHS-0701 DM93 Y127(3.13); Y129(3.47); Y76(8.14)  LDD0268  [8]
 LDCM0107  IAA HeLa H80(0.00); H12(0.00); H258(0.00); H259(0.00)  LDD0221  [11]
 LDCM0123  JWB131 DM93 Y129(1.28); Y68(0.90); Y76(0.96)  LDD0285  [7]
 LDCM0124  JWB142 DM93 Y129(0.72); Y43(1.50); Y68(0.62); Y76(1.06)  LDD0286  [7]
 LDCM0125  JWB146 DM93 Y129(1.17); Y68(0.81); Y76(1.28)  LDD0287  [7]
 LDCM0126  JWB150 DM93 Y129(3.64); Y43(16.47); Y68(6.44); Y76(4.81)  LDD0288  [7]
 LDCM0127  JWB152 DM93 Y43(15.12); Y68(2.95); Y76(4.05)  LDD0289  [7]
 LDCM0128  JWB198 DM93 Y129(0.78); Y68(0.96); Y76(1.30)  LDD0290  [7]
 LDCM0129  JWB202 DM93 Y68(0.83); Y76(1.03)  LDD0291  [7]
 LDCM0130  JWB211 DM93 Y43(5.24); Y68(1.20); Y76(2.07)  LDD0292  [7]
 LDCM0109  NEM HeLa H80(0.00); H12(0.00)  LDD0223  [11]
 LDCM0019  Staurosporine Hep-G2 12.00  LDD0083  [15]
 LDCM0110  W12 Hep-G2 W208(1.14)  LDD0237  [9]
 LDCM0112  W16 Hep-G2 W208(1.16)  LDD0239  [9]
 LDCM0113  W17 Hep-G2 K210(0.91); W208(0.91)  LDD0240  [9]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Galactose-1-phosphate uridylyltransferase (GALT) Galactose-1-phosphate uridylyltransferase type 1 family P07902
NAD(P)H dehydrogenase [quinone] 1 (NQO1) NAD(P)H dehydrogenase (quinone) family P15559
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Inhibitor of growth protein 1 (ING1) ING family Q9UK53

The Drug(s) Related To This Target

Approved
Click To Hide/Show 10 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Cannabidiol Small molecular drug DB09061
Cisplatin Small molecular drug DB00515
Dicoumarol Small molecular drug DB00266
Doxorubicin Small molecular drug DB00997
Flavin Adenine Dinucleotide Small molecular drug DB03147
Menadione Small molecular drug DB00170
Phenytoin Small molecular drug DB00252
Vitamin E Small molecular drug DB00163
Alpha-tocopherol Succinate . DB14001
D-alpha-tocopherol Acetate . DB14002
Phase 2
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Arq 761 . D0DR0P
Bioe-743 . D0RI4I
Coenzyme Q10 Analog . D0MM6A
Investigative
Click To Hide/Show 34 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
2-benzyl-1-hydroxy-3h-benzo[F]Chromen-3-one Small molecular drug D09ITX
3-(3,4-dimethylbenzyl)-4-hydroxy-2h-chromen-2-one Small molecular drug D06BHJ
3-benzyl-4-hydroxy-2h-benzo[H]Chromen-2-one Small molecular drug D03CDH
3-benzyl-4-hydroxy-2h-chromen-2-one Small molecular drug D09FMZ
3-benzyl-4-hydroxy-6,7-dimethyl-2h-chromen-2-one Small molecular drug D08XJX
4-amino-2h-chromen-2-one Small molecular drug D0B4GV
4-hydroxy-3-(1-naphthylmethyl)-2h-chromen-2-one Small molecular drug D09CYJ
4-hydroxy-3-(2-naphthylmethyl)-2h-chromen-2-one Small molecular drug D0H4YP
Bishydroxy[2h-1-benzopyran-2-one,1,2-benzopyrone] Small molecular drug D0H1BY
Bishydroxy[2h-1-benzopyran-2-one12-benzopyrone] Small molecular drug DB04392
Cibacron Blue Small molecular drug DB02633
Duroquinone Small molecular drug D01WPJ
Es-936 Small molecular drug D0GE8S
Ethyl Bis(4-hydroxy-2-oxo-2h-chromen-3-yl)Acetate Small molecular drug D02ONP
Flavin-adenine Dinucleotide Small molecular drug D00IMW
Nsc-106080 Small molecular drug D0J3RB
Nsc-106547 Small molecular drug D05GWI
Nsc-2113 Small molecular drug D07DGS
Nsc-224124 Small molecular drug D07MGN
Nsc-275420 Small molecular drug D0E2LU
Nsc-316158 Small molecular drug D0AN7U
Nsc-339580 Small molecular drug D0VB8K
Nsc-339583 Small molecular drug D0L3VV
Nsc-354279 Small molecular drug D00SRM
Nsc-621351 Small molecular drug D0A5TD
Nsc-645808 Small molecular drug D0E0DQ
Nsc-645827 Small molecular drug D0T4RW
Nsc-65069 Small molecular drug D0O8YZ
Nsc-73410 Small molecular drug D07JNQ
Nsc-99528 Small molecular drug D0M0WT
Rh-1 Small molecular drug DB04090
3-(Hydroxymethyl)-1-methyl-5-(2-methylaziridin-1-yl)-2-phenyl-1h-indole-47-dione . DB07385
3-hydroxymethyl-5-aziridinyl-1methyl-2-[1h-indole-47-dione]-propanol . DB02395
5-methoxy-12-dimethyl-3-(Phenoxymethyl)Indole-47-dione . DB03626

References

1 Design and synthesis of tailored human caseinolytic protease P inhibitors. Chem Commun (Camb). 2018 Aug 28;54(70):9833-9836. doi: 10.1039/c8cc05265d.
Mass spectrometry data entry: PXD010277
2 Low-Toxicity Sulfonium-Based Probes for Cysteine-Specific Profiling in Live Cells. Anal Chem. 2022 Mar 15;94(10):4366-4372. doi: 10.1021/acs.analchem.1c05129. Epub 2022 Mar 4.
3 Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors. J Med Chem. 2022 Aug 11;65(15):10408-10418. doi: 10.1021/acs.jmedchem.2c00272. Epub 2022 Jul 26.
4 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
5 2H-Azirine-Based Reagents for Chemoselective Bioconjugation at Carboxyl Residues Inside Live Cells. J Am Chem Soc. 2020 Apr 1;142(13):6051-6059. doi: 10.1021/jacs.9b12116. Epub 2020 Mar 23.
6 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
7 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
8 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
9 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
10 Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer. J Proteome Res. 2018 Jan 5;17(1):63-75. doi: 10.1021/acs.jproteome.7b00329. Epub 2017 Nov 22.
Mass spectrometry data entry: PXD006095 , PXD006096
11 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
12 Differently Tagged Probes for Protein Profiling of Mitochondria. Chembiochem. 2019 May 2;20(9):1155-1160. doi: 10.1002/cbic.201800735. Epub 2019 Mar 26.
13 Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation. Cell Chem Biol. 2022 Dec 15;29(12):1709-1720.e7. doi: 10.1016/j.chembiol.2022.11.008. Epub 2022 Dec 6.
Mass spectrometry data entry: PXD038010
14 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
15 Comprehensive identification of staurosporine-binding kinases in the hepatocyte cell line HepG2 using Capture Compound Mass Spectrometry (CCMS). J Proteome Res. 2010 Feb 5;9(2):806-17. doi: 10.1021/pr9007333.
16 Cell-based proteome profiling of potential dasatinib targets by use of affinity-based probes. J Am Chem Soc. 2012 Feb 15;134(6):3001-14. doi: 10.1021/ja208518u. Epub 2012 Feb 1.