Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T52389
(Former ID: TTDC00200)
|
|||||
| Target Name |
Quinone reductase 1 (NQO1)
|
|||||
| Synonyms |
Qui reductase 1; QR1; Phylloquinone reductase; Phylloqui reductase; NMOR1; NAD(P)H:quinone oxidoreductase 1; NAD(P)H dehydrogenase [quinone] 1; Menadione reductase; DTD; DT-diaphorase 1; DT-diaphorase; DIA4; Azoreductase
Click to Show/Hide
|
|||||
| Gene Name |
NQO1
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 6 Target-related Diseases | + | ||||
| 1 | Choreiform disorder [ICD-11: 8A01] | |||||
| 2 | CNS anomalies syndrome [ICD-11: LD20] | |||||
| 3 | Inborn energy metabolism error [ICD-11: 5C53] | |||||
| 4 | Intellectual development disorder [ICD-11: LD90] | |||||
| 5 | Pancreatic cancer [ICD-11: 2C10] | |||||
| 6 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
Click to Show/Hide
|
|||||
| BioChemical Class |
NADH/NADPH oxidoreductase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 1.6.5.2
|
|||||
| Sequence |
MVGRRALIVLAHSERTSFNYAMKEAAAAALKKKGWEVVESDLYAMNFNPIISRKDITGKL
KDPANFQYPAESVLAYKEGHLSPDIVAEQKKLEAADLVIFQFPLQWFGVPAILKGWFERV FIGEFAYTYAAMYDKGPFRSKKAVLSITTGGSGSMYSLQGIHGDMNVILWPIQSGILHFC GFQVLEPQLTYSIGHTPADARIQILEGWKKRLENIWDETPLYFAPSSLFDLNFQAGFLMK KEVQDEEKNKKFGLSVGHHLGKSIPTDNQIKARK Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T38EQ6 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | ARQ 761 | Drug Info | Phase 2 | Pancreatic cancer | [2] | |
| 2 | BioE-743 | Drug Info | Phase 2 | Leigh syndrome | [3] | |
| 3 | Coenzyme Q10 analog | Drug Info | Phase 2 | Huntington disease | [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 29 Inhibitor drugs | + | ||||
| 1 | ARQ 761 | Drug Info | [2] | |||
| 2 | 2-Benzyl-1-hydroxy-3H-benzo[f]chromen-3-one | Drug Info | [5] | |||
| 3 | 3-(3,4-Dimethylbenzyl)-4-hydroxy-2H-chromen-2-one | Drug Info | [5] | |||
| 4 | 3-Benzyl-4-hydroxy-2H-benzo[h]chromen-2-one | Drug Info | [5] | |||
| 5 | 3-Benzyl-4-hydroxy-2H-chromen-2-one | Drug Info | [5] | |||
| 6 | 3-Benzyl-4-hydroxy-6,7-dimethyl-2H-chromen-2-one | Drug Info | [5] | |||
| 7 | 4-amino-2H-chromen-2-one | Drug Info | [6] | |||
| 8 | 4-Hydroxy-3-(1-naphthylmethyl)-2H-chromen-2-one | Drug Info | [5] | |||
| 9 | 4-Hydroxy-3-(2-naphthylmethyl)-2H-chromen-2-one | Drug Info | [5] | |||
| 10 | Bishydroxy[2h-1-Benzopyran-2-One,1,2-Benzopyrone] | Drug Info | [7] | |||
| 11 | Duroquinone | Drug Info | [7] | |||
| 12 | ES-936 | Drug Info | [8] | |||
| 13 | Ethyl Bis(4-hydroxy-2-oxo-2H-chromen-3-yl)acetate | Drug Info | [5] | |||
| 14 | Flavin-Adenine Dinucleotide | Drug Info | [7] | |||
| 15 | NSC-106080 | Drug Info | [9] | |||
| 16 | NSC-106547 | Drug Info | [10] | |||
| 17 | NSC-2113 | Drug Info | [10] | |||
| 18 | NSC-224124 | Drug Info | [10] | |||
| 19 | NSC-275420 | Drug Info | [10] | |||
| 20 | NSC-316158 | Drug Info | [10] | |||
| 21 | NSC-339580 | Drug Info | [10] | |||
| 22 | NSC-339583 | Drug Info | [10] | |||
| 23 | NSC-354279 | Drug Info | [10] | |||
| 24 | NSC-621351 | Drug Info | [9] | |||
| 25 | NSC-645808 | Drug Info | [10] | |||
| 26 | NSC-645827 | Drug Info | [10] | |||
| 27 | NSC-65069 | Drug Info | [9] | |||
| 28 | NSC-73410 | Drug Info | [10] | |||
| 29 | NSC-99528 | Drug Info | [9] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | BioE-743 | Drug Info | [3] | |||
| 2 | Coenzyme Q10 analog | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: RH 1 | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF HUMAN NAD[P]H-QUINONE OXIDOREDUCTASE CO WITH 2,5-diaziridinyl-3-hydroxyl-6-methyl-1,4-benzoquinone | PDB:1H66 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [11] |
| PDB Sequence |
AGRRALIVLA
10 HSERTSFNYA20 MKEAAAAALK30 KKGWEVVESD40 LYAMNFNPII50 SRKDITGKLK 60 DPANFQYPAE70 SVLAYKEGHL80 SPDIVAEQKK90 LEAADLVIFQ100 FPLQWFGVPA 110 ILKGWFERVF120 IGEFAYTYAA130 MYDKGPFRSK140 KAVLSITTGG150 SGSMYSLQGI 160 HGDMNVILWP170 IQSGILHFCG180 FQVLEPQLTY190 SIGHTPADAR200 IQILEGWKKR 210 LENIWDETPL220 YFAPSSLFDL230 NFQAGFLMKK240 EVQDEEKNKK250 FGLSVGHHLG 260 KSIPTDNQIK270 ARK
|
|||||
|
|
||||||
| Ligand Name: Bishydroxy[2h-1-Benzopyran-2-One,1,2-Benzopyrone] | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF THE H80R VARIANT OF NQO1 BOUND TO DICOUMAROL | PDB:5FUQ | ||||
| Method | X-ray diffraction | Resolution | 2.04 Å | Mutation | Yes | [12] |
| PDB Sequence |
MVGRRALIVL
10 AHSERTSFNY20 AMKEAAAAAL30 KKKGWEVVES40 DLYAMNFNPI50 ISRKDITGKL 60 KDPANFQYPA70 ESVLAYKEGR80 LSPDIVAEQK90 KLEAADLVIF100 QFPLQWFGVP 110 AILKGWFERV120 FIGEFAYTYA130 AMYDKGPFRS140 KKAVLSITTG150 GSGSMYSLQG 160 IHGDMNVILW170 PIQSGILHFC180 GFQVLEPQLT190 YSIGHTPADA200 RIQILEGWKK 210 RLENIWDETP220 LYFAPSSLFD230 LNFQAGFLMK240 KEVQDEEKNK250 KFGLSVGHHL 260 GKSIPTDNQI270 KAR
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Ubiquinone and other terpenoid-quinone biosynthesis | hsa00130 | Affiliated Target |
|
| Class: Metabolism => Metabolism of cofactors and vitamins | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 2.29E-01 | Radiality | 1.40E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 2.64E+02 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Ubiquinone and other terpenoid-quinone biosynthesis | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Vitamin K Metabolism | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Validated transcriptional targets of TAp63 isoforms | |||||
| WikiPathways | [+] 11 WikiPathways | + | ||||
| 1 | Estrogen metabolism | |||||
| 2 | Oxidative Stress | |||||
| 3 | Transcriptional activation by NRF2 | |||||
| 4 | NRF2 pathway | |||||
| 5 | Nuclear Receptors Meta-Pathway | |||||
| 6 | Aryl Hydrocarbon Receptor Pathway | |||||
| 7 | Apoptosis-related network due to altered Notch3 in ovarian cancer | |||||
| 8 | Metabolism of amino acids and derivatives | |||||
| 9 | Aryl Hydrocarbon Receptor | |||||
| 10 | Dopamine metabolism | |||||
| 11 | Arylhydrocarbon receptor (AhR) signaling pathway | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Therapeutic strategies for Leber's hereditary optic neuropathy: A current update. Intractable Rare Dis Res. 2013 November; 2(4): 130-135. | |||||
| REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | ClinicalTrials.gov (NCT02352896) Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome. U.S. National Institutes of Health. | |||||
| REF 5 | Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1). J Med Chem. 2009 Nov 26;52(22):7142-56. | |||||
| REF 6 | Coumarin-based inhibitors of human NAD(P)H:quinone oxidoreductase-1. Identification, structure-activity, off-target effects and in vitro human panc... J Med Chem. 2007 Dec 13;50(25):6316-25. | |||||
| REF 7 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 8 | Synthesis and evaluation of 3-aryloxymethyl-1,2-dimethylindole-4,7-diones as mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1) ... J Med Chem. 2007 Nov 15;50(23):5780-9. | |||||
| REF 9 | In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. | |||||
| REF 10 | In silico identification and biochemical characterization of novel inhibitors of NQO1. Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. | |||||
| REF 11 | Structure-based development of anticancer drugs: complexes of NAD(P)H:quinone oxidoreductase 1 with chemotherapeutic quinones. Structure. 2001 Aug;9(8):659-67. | |||||
| REF 12 | Identification of Novel Structural Hot-Spots for the Correction of Functional and Stability Defects in a Cancer-Associated Polymorphic Nadph:Quinone Oxidoreductase 1 from Sequence-Alignment Statistics. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.