Target Information
| Target General Information | Top | |||||
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| Target ID |
T75498
(Former ID: TTDC00138)
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| Target Name |
Quinone reductase 2 (NQO2)
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| Synonyms |
Quinone oxidoreductase 2; Qui reductase 2; QR2; NRH:quinone oxidoreductase 2; NRH:qui oxidoreductase 2; NQO2; NAD(P)H qui oxidoreductase 2
Click to Show/Hide
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| Gene Name |
NQO2
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Insomnia [ICD-11: 7A00-7A0Z] | |||||
| Function |
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones 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
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| BioChemical Class |
Diphenol donor oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.10.5.1
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| Sequence |
MAGKKVLIVYAHQEPKSFNGSLKNVAVDELSRQGCTVTVSDLYAMNLEPRATDKDITGTL
SNPEVFNYGVETHEAYKQRSLASDITDEQKKVREADLVIFQFPLYWFSVPAILKGWMDRV LCQGFAFDIPGFYDSGLLQGKLALLSVTTGGTAEMYTKTGVNGDSRYFLWPLQHGTLHFC GFKVLAPQISFAPEIASEEERKGMVAAWSQRLQTIWKEEPIPCTAHWHFGQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T28WZ9 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Melatonin | Drug Info | Approved | Insomnia | [2], [3], [4] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | NSC-645809 | Drug Info | Phase 2 | Breast cancer | [5] | |
| 2 | Prolarix | Drug Info | Phase 2 | Solid tumour/cancer | [6] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | CB1954 | Drug Info | Discontinued in Phase 2 | Solid tumour/cancer | [7] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 63 Inhibitor drugs | + | ||||
| 1 | Melatonin | Drug Info | [1] | |||
| 2 | NSC-645809 | Drug Info | [8] | |||
| 3 | Prolarix | Drug Info | [9] | |||
| 4 | CB1954 | Drug Info | [10] | |||
| 5 | 1,4-Dimethylquinolin-2(1H)-one | Drug Info | [11] | |||
| 6 | 10-Propargyl-5,8-Dideazafolic Acid | Drug Info | [10] | |||
| 7 | 2-iodo-melatonin | Drug Info | [11] | |||
| 8 | 3,4,5-Trimethoxy-4'-amino-trans-stilbene | Drug Info | [12] | |||
| 9 | 3,5-Dimethoxy-4'-amino-trans-stilbene | Drug Info | [12] | |||
| 10 | 5,6,8-Trimethoxy-1,4-dimethylquinolin-2(1H)-one | Drug Info | [11] | |||
| 11 | 5,6,8-Trimethoxy-4-methylquinolin-2(1H)-one | Drug Info | [11] | |||
| 12 | 5,8-dimethoxy-1,4-dimethylquinolin-2(1H)-one | Drug Info | [1] | |||
| 13 | 5,8-Dimethoxy-4-methylquinolin-2(1H)-one | Drug Info | [11] | |||
| 14 | 6,7,8-Trimethoxy-1,4-dimethylquinolin-2(1H)-one | Drug Info | [11] | |||
| 15 | 6,7,8-Trimethoxy-4-methylquinolin-2(1H)-one | Drug Info | [11] | |||
| 16 | 6,8-Dimethoxy-1,4-dimethylquinolin-2(1H)-one | Drug Info | [11] | |||
| 17 | 6,8-Dimethoxy-4-methylquinolin-2(1H)-one | Drug Info | [11] | |||
| 18 | 6-Methyl-[1,3]dioxolo[4,5-h]quinolin-8(9H)-one | Drug Info | [11] | |||
| 19 | 8-Methoxy-1,4-dimethylquinolin-2(1H)-one | Drug Info | [11] | |||
| 20 | decynium 22 | Drug Info | [13] | |||
| 21 | Flavin-Adenine Dinucleotide | Drug Info | [10] | |||
| 22 | NSC-106080 | Drug Info | [13] | |||
| 23 | NSC-115890 | Drug Info | [13] | |||
| 24 | NSC-204996 | Drug Info | [13] | |||
| 25 | NSC-238146 | Drug Info | [13] | |||
| 26 | NSC-300853 | Drug Info | [13] | |||
| 27 | NSC-306843 | Drug Info | [13] | |||
| 28 | NSC-356820 | Drug Info | [13] | |||
| 29 | NSC-381864 | Drug Info | [13] | |||
| 30 | NSC-637991 | Drug Info | [8] | |||
| 31 | NSC-637992 | Drug Info | [8] | |||
| 32 | NSC-637993 | Drug Info | [8] | |||
| 33 | NSC-637994 | Drug Info | [8] | |||
| 34 | NSC-640353 | Drug Info | [13] | |||
| 35 | NSC-640556 | Drug Info | [13] | |||
| 36 | NSC-640558 | Drug Info | [13] | |||
| 37 | NSC-640559 | Drug Info | [13] | |||
| 38 | NSC-640566 | Drug Info | [13] | |||
| 39 | NSC-640583 | Drug Info | [13] | |||
| 40 | NSC-645808 | Drug Info | [8] | |||
| 41 | NSC-645811 | Drug Info | [8] | |||
| 42 | NSC-645812 | Drug Info | [8] | |||
| 43 | NSC-645831 | Drug Info | [8] | |||
| 44 | NSC-645833 | Drug Info | [8] | |||
| 45 | NSC-645834 | Drug Info | [8] | |||
| 46 | NSC-645835 | Drug Info | [8] | |||
| 47 | NSC-645836 | Drug Info | [8] | |||
| 48 | NSC-649091 | Drug Info | [13] | |||
| 49 | NSC-660838 | Drug Info | [8] | |||
| 50 | NSC-660839 | Drug Info | [8] | |||
| 51 | NSC-660840 | Drug Info | [8] | |||
| 52 | NSC-660841 | Drug Info | [8] | |||
| 53 | NSC-665126 | Drug Info | [13] | |||
| 54 | NSC-669977 | Drug Info | [13] | |||
| 55 | NSC-676468 | Drug Info | [13] | |||
| 56 | NSC-677939 | Drug Info | [13] | |||
| 57 | NSC-693571 | Drug Info | [13] | |||
| 58 | NSC-77833 | Drug Info | [13] | |||
| 59 | NSC-78017 | Drug Info | [13] | |||
| 60 | NSC-78021 | Drug Info | [13] | |||
| 61 | NSC-86715 | Drug Info | [13] | |||
| 62 | NSC-99495 | Drug Info | [13] | |||
| 63 | NSC-99528 | Drug Info | [13] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Melatonin | Ligand Info | |||||
| Structure Description | Crystal structure of fad quinone reductase 2 in complex with melatonin at 1.4A | PDB:4QOG | ||||
| Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | Yes | [14] |
| PDB Sequence |
GKKVLIVYAH
11 QEPKSFNGSL21 KNVAVDELSR31 QGCTVTVSDL41 YAMNFEPRAT51 DKDITGTLSN 61 PEVFNYGVET71 HEAYKQRSLA81 SDITDEQKKV91 READLVIFQF101 PLYWFSVPAI 111 LKGWMDRVLC121 QGFAFDIPGF131 YDSGLLQGKL141 ALLSVTTGGT151 AEMYTKTGVN 161 GDSRYFLWPL171 QHGTLHFCGF181 KVLAPQISFA191 PEIASEEERK201 GMVAAWSQRL 211 QTIWKEEPIP221 CTAHWHFG
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Prazosin | Ligand Info | |||||
| Structure Description | X-ray Structural study of quinone reductase II inhibition by compounds with micromolar to nanomolar range IC50 values | PDB:3OWX | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [15] |
| PDB Sequence |
GKKVLIVYAH
11 QEPKSFNGSL21 KNVAVDELSR31 QGCTVTVSDL41 YAMNFEPRAT51 DKDITGTLSN 61 PEVFNYGVET71 HEAYKQRSLA81 SDITDEQKKV91 READLVIFQF101 PLYWFSVPAI 111 LKGWMDRVLC121 QGFAFDIPGF131 YDSGLLQGKL141 ALLSVTTGGT151 AEMYTKTGVN 161 GDSRYFLWPL171 QHGTLHFCGF181 KVLAPQISFA191 PEIASEEERK201 GMVAAWSQRL 211 QTIWKEEPIP221 CTAHWHF
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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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 Similarity Proteins
Human Tissue Distribution
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There is no similarity protein (E value < 0.005) for this target
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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.
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| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "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 | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 2 | 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: 224). | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | Melatonin and melatonergic drugs on sleep: possible mechanisms of action. Int J Neurosci. 2009;119(6):821-46. | |||||
| REF 5 | Role of human UDP-glucuronosyltransferases in the biotransformation of the triazoloacridinone and imidazoacridinone antitumor agents C-1305 and C-1311: highly selective substrates for UGT1A10. Drug Metab Dispos. 2012 Sep;40(9):1736-43. | |||||
| REF 6 | ClinicalTrials.gov (NCT00746590) Study of Anti-tumour Effects and Safety of Prolarix in Hepatocellular Carcinoma. U.S. National Institutes of Health. | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019051) | |||||
| REF 8 | Imidazoacridin-6-ones as novel inhibitors of the quinone oxidoreductase NQO2. Bioorg Med Chem Lett. 2010 May 1;20(9):2832-6. | |||||
| REF 9 | CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008. | |||||
| REF 10 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 11 | Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities. J Med Chem. 2009 Apr 9;52(7):1873-84. | |||||
| REF 12 | Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer. Bioorg Med Chem. 2010 Jul 15;18(14):5352-66. | |||||
| REF 13 | 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 14 | Crystal structure of fad quinone reductase 2 in complex with melatonin at 1.4A | |||||
| REF 15 | X-ray structural studies of quinone reductase 2 nanomolar range inhibitors. Protein Sci. 2011 Jul;20(7):1182-95. | |||||
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