NQO2

Summary

NQO2 (N-ribosyldihydronicotinamide:quinone dehydrogenase 2, HGNC:7856) is a protein-coding gene on chromosome 6p25.2, encoding Ribosyldihydronicotinamide dehydrogenase [quinone] (P16083). 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 synthes….

This gene encodes a member of the thioredoxin family of enzymes. It is a cytosolic and ubiquitously expressed flavoprotein that catalyzes the two-electron reduction of quinone substrates and uses dihydronicotinamide riboside as a reducing coenzyme. Mutations in this gene have been associated with neurodegenerative diseases and several cancers. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4835 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 47 total
• Phenotypes (HPO): 3
• Druggable target: yes — 45 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7856
Approved symbol	NQO2
Name	N-ribosyldihydronicotinamide:quinone dehydrogenase 2
Location	6p25.2
Locus type	gene with protein product
Status	Approved
Aliases	QR2, DHQV, DIA6
Ensembl gene	ENSG00000124588
Ensembl biotype	protein_coding
OMIM	160998
Entrez	4835

Gene structure

Transcript identifiers

Ensembl transcripts: 90 — 90 protein_coding

ENST00000338130, ENST00000380430, ENST00000380441, ENST00000380454, ENST00000380455, ENST00000380472, ENST00000397717, ENST00000426637, ENST00000606474, ENST00000892207, ENST00000892208, ENST00000892209, ENST00000892210, ENST00000892211, ENST00000892212, ENST00000892213, ENST00000892214, ENST00000892215, ENST00000892216, ENST00000892217, ENST00000892218, ENST00000892219, ENST00000892220, ENST00000892221, ENST00000892222, ENST00000892223, ENST00000892224, ENST00000892225, ENST00000892226, ENST00000892227, ENST00000892228, ENST00000892229, ENST00000892230, ENST00000892231, ENST00000892232, ENST00000892233, ENST00000892234, ENST00000892235, ENST00000892236, ENST00000892237, ENST00000892238, ENST00000892239, ENST00000892240, ENST00000892241, ENST00000929205, ENST00000929206, ENST00000929207, ENST00000929208, ENST00000929209, ENST00000929210, ENST00000929211, ENST00000929212, ENST00000929213, ENST00000929214, ENST00000929215, ENST00000929216, ENST00000929217, ENST00000929218, ENST00000929219, ENST00000929220, ENST00000929221, ENST00000929222, ENST00000929223, ENST00000929224, ENST00000929225, ENST00000929226, ENST00000929227, ENST00000929228, ENST00000929229, ENST00000952437, ENST00000952438, ENST00000952439, ENST00000952440, ENST00000952441, ENST00000952442, ENST00000952443, ENST00000952444, ENST00000952445, ENST00000952446, ENST00000952447, ENST00000952448, ENST00000952449, ENST00000952450, ENST00000952451, ENST00000952452, ENST00000952453, ENST00000952454, ENST00000952455, ENST00000952456, ENST00000952457

RefSeq mRNA: 4 — MANE Select: NM_000904 NM_000904, NM_001290221, NM_001290222, NM_001318940

CCDS: CCDS4481, CCDS75388

Canonical transcript exons

ENST00000380455 — 7 exons

Exon	Start	End
ENSE00000680401	3016884	3016985
ENSE00000847812	3012544	3012674
ENSE00001083962	3010025	3010189
ENSE00001398818	3019479	3019755
ENSE00001728408	2999894	3000085
ENSE00001777236	3006468	3006559
ENSE00003785120	3015530	3015643

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 97.69.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6852 / max 48.3036, expressed in 882 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65504	15.9179	1792
65505	13.3034	1704
65506	2.4246	1064
65499	1.6852	882
65507	0.9466	550
65508	0.5207	299

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland	UBERON:0001234	97.69	gold quality
left adrenal gland cortex	UBERON:0035825	97.62	gold quality
right adrenal gland	UBERON:0001233	97.46	gold quality
right adrenal gland cortex	UBERON:0035827	97.39	gold quality
adrenal cortex	UBERON:0001235	97.19	gold quality
adult mammalian kidney	UBERON:0000082	97.03	gold quality
triceps brachii	UBERON:0001509	96.47	gold quality
right lobe of liver	UBERON:0001114	96.18	gold quality
adrenal gland	UBERON:0002369	96.17	gold quality
gastrocnemius	UBERON:0001388	95.75	gold quality
apex of heart	UBERON:0002098	95.72	gold quality
nephron tubule	UBERON:0001231	95.59	gold quality
adult organism	UBERON:0007023	95.54	gold quality
right coronary artery	UBERON:0001625	95.40	gold quality
muscle of leg	UBERON:0001383	95.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.23	gold quality
right atrium auricular region	UBERON:0006631	94.56	gold quality
heart left ventricle	UBERON:0002084	94.46	gold quality
cardiac ventricle	UBERON:0002082	94.27	gold quality
kidney	UBERON:0002113	94.22	gold quality
left coronary artery	UBERON:0001626	94.19	gold quality
adipose tissue	UBERON:0001013	94.11	gold quality
descending thoracic aorta	UBERON:0002345	94.05	gold quality
connective tissue	UBERON:0002384	93.88	gold quality
blood	UBERON:0000178	93.86	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.86	gold quality
omental fat pad	UBERON:0010414	93.85	gold quality
peritoneum	UBERON:0002358	93.82	gold quality
coronary artery	UBERON:0001621	93.80	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.79	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6524	no	189.63
E-GEOD-109979	no	173.69
E-MTAB-8271	no	162.96
E-GEOD-124858	no	107.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUND, NFE2L2, SP1, SP3

miRNA regulators (miRDB)

15 targeting NQO2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-4448	97.04	66.22	752
HSA-MIR-6772-3P	97.04	65.89	784

Literature-anchored findings (GeneRIF, showing 35)

• polymorphisms associated with idiopathic Parkinson’s disease (PMID:11688992)
• A significant difference was found between alcoholic patients and controls in genotype frequency at an insertion/deletion site in the promoter region of the NQO2 gene (p = 0.0014). (PMID:12960511)
• the level of NQO2 mRNA is low in AGR patients compared with the control group. Such a reduction in message suggests that the NQO2 gene may be involved in the development of clozapine-induced AGR. (PMID:14617031)
• NQO2 gene may confer susceptibility to a certain form of schizophrenia. (PMID:14639047)
• the NQO2 gene is differentially expressed by the polymorphic promoters in human cells transfected with NQO2 gene reporter constructs. Alterations in NQO2 activity might be an important factor in susceptibility to Parkinson’s disease. (PMID:15451063)
• We propose that induction of NQO2 may relate to the observed increased expression of p53 that, in turn, contributes to the observed suppression of cell growth in both melanoma cell lines. (PMID:15993843)
• the nicotinamide adenine dinucleotide phosphate reduced-diaphorase interneurons in the human striatum. (PMID:16025450)
• The results combined demonstrated that Nrf2 associates with JunD, binds to ARE at nucleotide -1433, and regulates human NQO2 gene expression and induction in response to antioxidants. (PMID:16545679)
• an apparent association between an NQO2 exon 3 single-nucleotide polymorphism and lower enzymatic activity (PMID:17332305)
• The crystal structure of melatonin and 2-iodomelatonin in complex with QR2 provide a detailed description of the enzyme active site; the design of inhibitors of the enzyme might be instrumental in discriminating the role of MT1, MT2 and QR2/MT3 (PMID:18254726)
• Parkinson’s disease patients were analyzed for NQO2 gene promoter polymorphisms. Three allelic variants were I-29, I-16 and D. The association of the D promoter with Parkinson’s disease may be due to an increase in expression of the NQO2 gene. (PMID:18314446)
• This first structural analysis of hQR2 should enable to better understand the biological role of melatonin on this enzyme . (PMID:18502195)
• We observed a nominal significant association between the rs1143684 NQO2 polymorphism and the trajectory of delayed memory recall over time (p=0.029). No other associations were seen with the decline of other cognitive abilities. (PMID:18538895)
• Quinone reductase 2 is a catechol quinone reductase. quinone reductase 2 could play important roles in the regulation of catecholamine oxidation processes that may be involved in the etiology of Parkinson disease. (PMID:18579530)
• nmr studies of QR2 catalytic reaction were performed; results led to conclusion that melatonin is not cleaved to form N1-acetyl-N2-formyl-5-methoxykynurenine by a catalytically active QR2, indicating melatonin is neither a substrate nor a co-substrate (PMID:18826489)
• NQO2 is a susceptibility gene for breast carcinogenesis. (PMID:19351655)
• Our findings challenge the previous assumption that the NQo2 I-16 allele is stable only when paired with another I-16 allele (PMID:19495956)
• The first European study of the SOD2, SOD3, NQO1, and NQO2 roles in pancreatic cancer etiology did not find significant associations. (PMID:20966810)
• The NQO1 609C>T TT genotype and T allele were significantly associated with increased risk for gastric cancer (GC), whereas NQO2 -3423G>A polymorphism did not show any association with GC. (PMID:21294640)
• Results suggest that NQO2, SOD2 and SOD3 may significantly modify prognosis of breast cancer patients. (PMID:21351093)
• NQO2 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• Selective inhibition of NQO2 over NQO1 can be attributed to the bulky aminoalkylamino substituent at the 5-position, which blocks entrance of the indolequinones into the NQO1 active site. (PMID:21718050)
• results suggest that the increase in hippocampal QR2 might be a cause of AD or might promote the progression of AD by causing an increase in the toxic quinone levels and consequent loss of cognitive function. (PMID:21803122)
• both NQO1 and NQO2 modulate the efficacy of AC therapy and that NQO2 is associated with tamoxifen toxicity. (PMID:21946896)
• results indicate a role of NQO2 in the control of AKT/GSK-3beta/cyclin D1 and highlight the involvement of NQO2 in degradation of cyclin D1, as part of mechanism of chemoprevention by resveratrol (PMID:22266466)
• NQO1 609C>T and NQO2 -3423G>A polymorphisms do not seem to play any significant role in susceptibility or prognosis of EC in north Indian population. (PMID:22770696)
• Diplotypes of NQO1 (exon 4 and 6), C-T (OR = 1.56, Pc = 0.007) and T-T (OR = 0.011, Pc = 3.86) was associated with an increased risk for prostate cancer (PCa). NQO2 and MTHFR did not show any risk with PCa. (PMID:23054000)
• This first structure of a reduced quinone reductase shows that reduction of the FAD cofactor and binding of a specific inhibitor lead to global changes in NQO2 structure and is consistent with a functional role for NQO2 as a flavin redox switch. (PMID:23471972)
• NQO2-L47 is less stable towards proteolytic digestion and thermal denaturation than NQO2-F47. (PMID:24631540)
• In patients with Alzheimer’s disease, QR2 is overexpressed in the insular cotex. (PMID:26609153)
• The ontogeny and population variability of human hepatic dihydronicotinamide riboside:quinone oxidoreductase (NQO2). (PMID:28346733)
• these data suggest that the overexpression of QR2 in brain cells in the presence of catechol quinones might lead to reactive oxygen species-induced cell death via the rapid conversion of superoxide radicals into hydrogen peroxide and then into highly reactive hydroxyl radicals (PMID:29526807)
• Cancer-associated variants of human NQO1: impacts on inhibitor binding and cooperativity. (PMID:31431515)
• An Axis between the Long Non-Coding RNA HOXA11-AS and NQOs Enhances Metastatic Ability in Oral Squamous Cell Carcinoma. (PMID:36142607)
• Polymorphisms and Pharmacogenomics of NQO2: The Past and the Future. (PMID:38254976)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nqo2	ENSMUSG00000046949
rattus_norvegicus	Nqo2	ENSRNOG00000017820
rattus_norvegicus	AABR07044714.1	ENSRNOG00000053936

Paralogs (1): NQO1 (ENSG00000181019)

Protein

Protein identifiers

Ribosyldihydronicotinamide dehydrogenase [quinone] — P16083 (reviewed: P16083)

Alternative names: NRH dehydrogenase [quinone] 2, NRH:quinone oxidoreductase 2, Quinone reductase 2

All UniProt accessions (5): A2A2U4, P16083, Q5TD05, Q5TD07, U3KQG7

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Activity regulation. Inhibited by melatonin, resveratrol and 5-hydroxytryptamine.

Cofactor. Binds 1 zinc ion per subunit.

Miscellaneous. Uses dihydronicotinamide riboside (NRH) rather than NAD(P)H as an electron donor.

Similarity. Belongs to the NAD(P)H dehydrogenase (quinone) family.

RefSeq proteins (4): NP_000895, NP_001277150, NP_001277151, NP_001305869 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003680	Flavodoxin_fold	Domain
IPR029039	Flavoprotein-like_sf	Homologous_superfamily
IPR051545	NAD(P)H_dehydrogenase_qn	Family

Pfam: PF02525

Enzyme classification (BRENDA):

• EC 1.10.5.1 — ribosyldihydronicotinamide dehydrogenase (quinone) (BRENDA: 7 organisms, 82 substrates, 281 inhibitors, 35 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MENADIONE	0.0016–0.0252	7
N-BENZYL DIHYDRONICOTINAMIDE	0.0113–0.0602	5
DIHYDROBENZYLNICOTINAMIDE	0.02–0.0608	4
2,6-DICHLOROPHENOLINDOPHENOL	0.007–0.019	3
17BETA-17-HYDROXYESTR-1(10)-ENE-3,4-DIONE	0.0008	1
3-(4,5-DIMETHYLTHIAZAOL-2-YL)-2,5-DIPHENYLTETRAZ	0.012	1
5-(AZIRIDIN-1-YL)-2,4-DINITROBENZAMIDE	0.061	1
CB 1954	0.26	1
COENZYME Q0	0.0137	1
COENZYME Q1	0.0517	1
COENZYME Q2	0.0387	1
DIHYDRONICOTINAMIDE RIBOSIDE	0.028	1
ESTRADIOL-3,4-QUINONE	—	1
MENADIONE/3-(4,5-DIMETHYLTHIAZAOL-2-YL)-2,5-DIPH	0.0023	1
METHYL RED	0.0047	1

Catalyzed reactions (Rhea), 1 shown:

• 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone + H(+) = beta-nicotinamide D-riboside + a quinol (RHEA:12364)

UniProt features (47 total): binding site 11, helix 11, strand 9, turn 6, sequence variant 5, modified residue 2, chain 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

68 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4FGL	X-RAY DIFFRACTION	1.2
4FGJ	X-RAY DIFFRACTION	1.35
4QOD	X-RAY DIFFRACTION	1.35
4QOG	X-RAY DIFFRACTION	1.4
5LBY	X-RAY DIFFRACTION	1.4
5LBZ	X-RAY DIFFRACTION	1.4
4FGK	X-RAY DIFFRACTION	1.4
3TEM	X-RAY DIFFRACTION	1.45
4QOE	X-RAY DIFFRACTION	1.45
4U7H	X-RAY DIFFRACTION	1.48
1SG0	X-RAY DIFFRACTION	1.5
1XI2	X-RAY DIFFRACTION	1.5
2QWX	X-RAY DIFFRACTION	1.5
3UXE	X-RAY DIFFRACTION	1.5
4XDG	X-RAY DIFFRACTION	1.5
3UXH	X-RAY DIFFRACTION	1.53
4QOF	X-RAY DIFFRACTION	1.55
4QOI	X-RAY DIFFRACTION	1.55
3NFR	X-RAY DIFFRACTION	1.57
3NHL	X-RAY DIFFRACTION	1.57
2QX8	X-RAY DIFFRACTION	1.6
3O2N	X-RAY DIFFRACTION	1.6
4QOH	X-RAY DIFFRACTION	1.6
2QX4	X-RAY DIFFRACTION	1.65
3NHW	X-RAY DIFFRACTION	1.65
5LBU	X-RAY DIFFRACTION	1.65
3NHP	X-RAY DIFFRACTION	1.7
3TE7	X-RAY DIFFRACTION	1.7
2QX6	X-RAY DIFFRACTION	1.75
3FW1	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16083-F1	98.17	0.99

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (11): 12; 201; 223; 18–21; 104–107; 127–129; 148–151; 156; 174; 178; 194

Post-translational modifications (2): 80, 197

Mutagenesis-validated functional residues (1):

Position	Phenotype
162	loss of activity toward cb1954, no effect toward menadione.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-211945	Phase I - Functionalization of compounds

MSigDB gene sets: 168 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_KETONE_METABOLIC_PROCESS, chr6p25, CAIRO_HEPATOBLASTOMA_DN, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_NAD_P_H, KAAB_FAILED_HEART_VENTRICLE_DN, ACEVEDO_LIVER_CANCER_UP, GCM_BECN1, GRADE_COLON_AND_RECTAL_CANCER_UP, GOBP_QUINONE_METABOLIC_PROCESS, MARSON_BOUND_BY_FOXP3_UNSTIMULATED

GO Biological Process (1): quinone catabolic process (GO:1901662)

GO Molecular Function (13): dihydronicotinamide riboside quinone reductase activity (GO:0001512), NAD(P)H dehydrogenase (quinone) activity (GO:0003955), zinc ion binding (GO:0008270), electron transfer activity (GO:0009055), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on other nitrogenous compounds as donors (GO:0016661), chloride ion binding (GO:0031404), protein homodimerization activity (GO:0042803), FAD binding (GO:0071949), melatonin binding (GO:1904408), resveratrol binding (GO:1905594), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Biological oxidations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
cellular anatomical structure	3
ketone catabolic process	1
quinone metabolic process	1
oxidoreductase activity, acting on diphenols and related substances as donors	1
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	1
transition metal ion binding	1
molecular_function	1
catalytic activity	1
oxidoreductase activity	1
anion binding	1
identical protein binding	1
protein dimerization activity	1
flavin adenine dinucleotide binding	1
cation binding	1
nuclear lumen	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NQO2	CRYZ	Q08257	645
NQO2	CYP19A1	P11511	640
NQO2	ABL1	P00519	541
NQO2	PALB2	Q86YC2	504
NQO2	ARHGEF5	Q12774	491
NQO2	B3GAT2	Q9NPZ5	485
NQO2	GPR50	Q13585	479
NQO2	GCLC	P48506	462
NQO2	COMT	P21964	454
NQO2	MTNR1A	P48039	446
NQO2	SULT2B1	O00204	441
NQO2	ASMT	P46597	437
NQO2	AANAT	Q16613	430
NQO2	TCIM	Q9NR00	428
NQO2	NOX1	Q9Y5S8	425

IntAct

49 interactions, top by confidence:

A	B	Type	Score
NQO2	GORASP2	psi-mi:“MI:0915”(physical association)	0.740
NQO2	LRRC7	psi-mi:“MI:0915”(physical association)	0.720
LRRC7	NQO2	psi-mi:“MI:0915”(physical association)	0.720
PPP2R3A	WTIP	psi-mi:“MI:0914”(association)	0.640
NQO2	EFHC1	psi-mi:“MI:0915”(physical association)	0.560
NQO2	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
NQO2	SPG21	psi-mi:“MI:0915”(physical association)	0.560
HSCB	NQO2	psi-mi:“MI:0914”(association)	0.550
HSCB	NQO2	psi-mi:“MI:0915”(physical association)	0.550
	NQO2	psi-mi:“MI:0915”(physical association)	0.500
	TK2	psi-mi:“MI:0915”(physical association)	0.400
PA	NQO2	psi-mi:“MI:0915”(physical association)	0.370
DGCR6	NQO2	psi-mi:“MI:0915”(physical association)	0.370
RHOB	NQO2	psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
HLA-A	AIP	psi-mi:“MI:0914”(association)	0.350
NQO2	NSF	psi-mi:“MI:0914”(association)	0.350
RNF166	WASL	psi-mi:“MI:0914”(association)	0.350
GATA2	EFCAB5	psi-mi:“MI:0914”(association)	0.350
Smad6	DDX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): NQO2 (Two-hybrid), LRRC7 (Two-hybrid), NQO2 (Affinity Capture-RNA), NQO2 (Affinity Capture-RNA), GORASP2 (Two-hybrid), NQO2 (Synthetic Lethality), NQO2 (Affinity Capture-RNA), NQO2 (Affinity Capture-MS), NQO2 (Two-hybrid), NQO2 (Two-hybrid), NQO2 (Two-hybrid), NQO2 (Two-hybrid), DDIT4L (Two-hybrid), NQO2 (Affinity Capture-MS), NQO2 (Co-purification)

ESM2 similar proteins: A2VCW9, A2Y3Q5, A4IG42, A5GAC6, A8E657, B5EGQ4, O57478, O64765, P05982, P08509, P11413, P11605, P15559, P16083, P17570, P22315, P22830, P34913, P36859, P37830, P39865, P39866, P39868, P52788, P54233, P97355, Q13057, Q14032, Q1L8D2, Q29492, Q3SZA5, Q3YA36, Q5RBB9, Q5RD31, Q64669, Q64FW2, Q6AY80, Q6DHQ3, Q6ING7, Q6JQN1

Diamond homologs: A0A481WNM5, A1A795, A1JS77, A4W6F2, A8FA13, B1M4X4, B7LVT7, B7MAG9, P05982, P0AEY5, P0AEY6, P0AEY7, P15559, P16083, Q1RGF2, Q28QS5, Q5RBB9, Q5RD31, Q64669, Q6AY80, Q88EC8, Q8CHK7, Q92DN4, Q9JI75, A1AGN7, A4WFE5, A5EF62, A7ME22, A7Z8S7, A7ZHD9, A7ZSM7, A7ZVZ8, A8A5F9, A8ALQ5, A8AQP1, A9MQG7, B1IPB3, B1IRD0, B1LFY0, B1X6K1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

47 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1622 predictions. Top by Δscore:

Variant	Effect	Δscore
6:3000084:AGG:A	donor_loss	1.0000
6:3000086:GTGA:G	donor_loss	1.0000
6:3004655:GGGA:G	donor_gain	1.0000
6:3004657:GA:G	donor_gain	1.0000
6:3015528:A:AG	acceptor_gain	1.0000
6:3015529:G:GG	acceptor_gain	1.0000
6:3016879:TGCA:T	acceptor_loss	1.0000
6:3016881:CA:C	acceptor_loss	1.0000
6:3016882:AG:A	acceptor_gain	1.0000
6:3016883:GG:G	acceptor_gain	1.0000
6:3000081:GGAAG:G	donor_gain	0.9900
6:3000082:GAAG:G	donor_gain	0.9900
6:3000082:GAAGG:G	donor_gain	0.9900
6:3000086:G:GG	donor_gain	0.9900
6:3000087:T:G	donor_loss	0.9900
6:3004595:A:G	donor_gain	0.9900
6:3004612:G:GT	donor_gain	0.9900
6:3004654:GGGGA:G	donor_gain	0.9900
6:3004656:GGA:G	donor_gain	0.9900
6:3006462:TTCCA:T	acceptor_loss	0.9900
6:3006463:TCCAG:T	acceptor_loss	0.9900
6:3006464:CCAGA:C	acceptor_loss	0.9900
6:3006465:CAGAT:C	acceptor_loss	0.9900
6:3006466:A:AC	acceptor_loss	0.9900
6:3006466:A:AG	acceptor_gain	0.9900
6:3006467:G:GG	acceptor_gain	0.9900
6:3006557:C:T	donor_gain	0.9900
6:3006557:CAG:C	donor_loss	0.9900
6:3006560:G:T	donor_loss	0.9900
6:3010190:G:GA	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000146700 (6:3014974 A>G), RS1000386937 (6:3000839 C>G), RS1000520002 (6:3014716 A>G), RS1000538816 (6:3006269 GA>G), RS1000602487 (6:3011408 G>A), RS1000659245 (6:3011749 A>C), RS1000744898 (6:3017342 G>A,T), RS1000751454 (6:3001936 T>C), RS1001163536 (6:3005077 G>A,T), RS1001833860 (6:3011295 G>A), RS1001892551 (6:3011240 A>G), RS1001964145 (6:3017016 G>A), RS1001997823 (6:3016570 T>A), RS1002071421 (6:3016827 C>T), RS1002181315 (6:3011030 C>T)

Disease associations

OMIM: gene MIM:160998 | disease phenotypes: MIM:167000

GenCC curated gene-disease

Mondo (1): ovarian cancer (MONDO:0008170)

Orphanet (1): Rare ovarian cancer (Orphanet:213500)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0003002	Breast carcinoma

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_1631	Blood protein levels	4.000000e-64
GCST009733_100	Urinary metabolite levels in chronic kidney disease	1.000000e-29
GCST009733_36	Urinary metabolite levels in chronic kidney disease	3.000000e-88

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3959 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

45 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 492,293 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL2	PRAZOSIN	4	31,107
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL3187723	BINIMETINIB	4	7,280
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3353410	OSIMERTINIB	4	8,898
CHEMBL3402762	TEPOTINIB	4	1,276
CHEMBL3989868	TUCATINIB	4	3,159
CHEMBL45	MELATONIN	4	56,417
CHEMBL506	PRIMAQUINE	4	10,279
CHEMBL535	SUNITINIB	4	79,020
CHEMBL76	CHLOROQUINE	4	58,679
CHEMBL941	IMATINIB	4	111,611
CHEMBL1241855	RIGOSERTIB	3	1,544
CHEMBL165	RESVERATROL	3	60,144
CHEMBL1908391	MASITINIB	3	2,808
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL3334567	SAVOLITINIB	3	1,199
CHEMBL3426621	RIPASUDIL	3
CHEMBL38380	FASUDIL	3
CHEMBL48361	DABIGATRAN	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL1232461	MOLIBRESIB	2
CHEMBL1614713	CC-401	2
CHEMBL1822792	MK-2461	2
CHEMBL206834	BAFETINIB	2
CHEMBL2386889	SCH-900776	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1143684	Efficacy	3	cyclophosphamide;doxorubicin	Breast Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1143684	NQO2	3	1.00	1	cyclophosphamide;doxorubicin

Binding affinities (BindingDB)

21 measured of 39 human assays (41 total across all organisms); most potent 21 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Melatonin,2-Iodo	KI	0.01 nM
14C-5-hydroxy tryptamine creatinine disulfate	KI	1.2 nM
casimiroin analogue, 1p	IC50	100 nM
N-Acetyltryptamine,5-Hydroxy	KI	223 nM
3-bromo-6-(pyridin-3-yl)-5-(pyridin-4-yl)pyridin-2-amine	KI	300 nM	US-10253017: Derivatives of 2-aminopyridine as adenosine A2B receptor antagonists and ligands of the melatonin MT3 receptors
2-(dimethylamino)-4,5,6,7-tetrabromo-1H-benzimidazole	IC50	484 nM
3-chloro-6-(pyridin-3-yl)-5-(pyridin-4-yl)pyridin-2-amine	KI	500 nM	US-10253017: Derivatives of 2-aminopyridine as adenosine A2B receptor antagonists and ligands of the melatonin MT3 receptors
casimiroin analogue, 1r	IC50	760 nM
casimiroin analogue, 1j	IC50	960 nM
casimiroin analogue, 1l	IC50	960 nM
casimiroin analogue, 1b	IC50	1250 nM
casimiroin analogue, 1f	IC50	2020 nM
casimiroin analogue, 1n	IC50	2720 nM
casimiroin	IC50	3920 nM
3-chloro-5-(3-fluoropyridin-4-yl)-6-(pyridin-3-yl)pyridin-2-amine	KI	4800 nM	US-10253017: Derivatives of 2-aminopyridine as adenosine A2B receptor antagonists and ligands of the melatonin MT3 receptors
casimiroin analogue, 1q	IC50	5680 nM
casimiroin analogue, 1h	IC50	5760 nM
casimiroin analogue, 1o	IC50	14800 nM
casimiroin analogue, 1m	IC50	18500 nM
casimiroin analogue, 1k	IC50	26800 nM
casimiroin analogue, 1g	IC50	31500 nM

ChEMBL bioactivities

403 potent at pChembl≥5 of 463 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.06	Ki	0.088	nM	CHEMBL300056
10.05	IC50	0.08913	nM	CHEMBL300056
9.89	Ki	0.13	nM	CHEMBL300728
9.89	IC50	0.1288	nM	CHEMBL300728
9.74	Ki	0.18	nM	CHEMBL52559
9.70	IC50	0.1995	nM	CHEMBL52559
9.52	IC50	0.302	nM	CHEMBL511675
9.52	Ki	0.3	nM	CHEMBL300728
9.51	Ki	0.31	nM	CHEMBL53622
9.51	IC50	0.309	nM	CHEMBL53622
9.41	IC50	0.39	nM	CHEMBL1770214
8.96	Ki	1.1	nM	CHEMBL300195
8.92	IC50	1.202	nM	CHEMBL300195
8.57	IC50	2.7	nM	CHEMBL504585
8.55	Ki	2.8	nM	CHEMBL33700
8.55	IC50	2.818	nM	CHEMBL33700
8.52	IC50	3.02	nM	CHEMBL457126
8.52	IC50	3	nM	CHEMBL6074469
8.40	Kd	4	nM	PACRITINIB
8.39	IC50	4.1	nM	CHEMBL1945729
8.31	IC50	4.9	nM	CHEMBL1738752
8.30	IC50	5	nM	CHEMBL6082944
8.22	IC50	6	nM	CHEMBL8602
8.21	Ki	6.1	nM	CHEMBL55084
8.19	Ki	6.5	nM	IODOMELATONIN
8.11	IC50	7.762	nM	CHEMBL465378
8.11	IC50	7.7	nM	CHEMBL6078562
8.11	IC50	7.8	nM	PRAZOSIN
8.05	IC50	9	nM	CHEMBL124254
8.04	Ki	9.09	nM	CHEMBL134447
8.04	IC50	9.12	nM	CHEMBL457992
8.04	IC50	9.1	nM	CHEMBL457992
8.00	IC50	10	nM	CHEMBL4514167
7.96	IC50	10.96	nM	CHEMBL457541
7.96	IC50	10.96	nM	CHEMBL493424
7.92	IC50	12.02	nM	CHEMBL455339
7.89	IC50	13	nM	CHEMBL1967497
7.85	IC50	14.13	nM	CHEMBL457539
7.85	IC50	14.13	nM	CHEMBL495399
7.85	IC50	14	nM	CHEMBL1836819
7.84	IC50	14.5	nM	CHEMBL3770674
7.82	IC50	15.2	nM	CHEMBL3770366
7.82	IC50	15	nM	CHEMBL4435240
7.80	IC50	15.85	nM	CHEMBL446329
7.80	IC50	16	nM	CHEMBL125082
7.77	IC50	17	nM	CHEMBL8150
7.75	IC50	18	nM	CHEMBL1237241
7.75	IC50	18	nM	CHEMBL456727
7.74	IC50	18.2	nM	CHEMBL456727
7.74	IC50	18.2	nM	CHEMBL494566

PubChem BioAssay actives

391 with measured affinity, of 898 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[2-(2-iodo-5-methoxy-1-methyl-4-nitroindol-3-yl)ethyl]acetamide	107724: Inhibition of 2-[125I]iodomelatonin binding to Melatonin receptor 3 (MT3) of Syrian hamster brain membrane	ki	0.0001	uM
N-[2-(2-iodo-5-methoxy-1-methylindol-3-yl)ethyl]acetamide	107724: Inhibition of 2-[125I]iodomelatonin binding to Melatonin receptor 3 (MT3) of Syrian hamster brain membrane	ki	0.0001	uM
N-[2-(2-iodo-5-methoxy-4-nitro-1H-indol-3-yl)ethyl]acetamide	107724: Inhibition of 2-[125I]iodomelatonin binding to Melatonin receptor 3 (MT3) of Syrian hamster brain membrane	ki	0.0002	uM
methyl N-[3-(2-acetamidoethyl)-2-iodo-1H-indol-5-yl]carbamate	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0003	uM
N-[2-(5-methoxy-1-methyl-4-nitroindol-3-yl)ethyl]acetamide	107724: Inhibition of 2-[125I]iodomelatonin binding to Melatonin receptor 3 (MT3) of Syrian hamster brain membrane	ki	0.0003	uM
methyl N-[8-(2-acetamidoethyl)naphthalen-2-yl]carbamate	594258: Binding affinity to human low affinity melatonin (MT3) site of quinone reductase 2	ic50	0.0004	uM
N-[2-(5-methoxy-4-nitro-1H-indol-3-yl)ethyl]acetamide	107724: Inhibition of 2-[125I]iodomelatonin binding to Melatonin receptor 3 (MT3) of Syrian hamster brain membrane	ki	0.0011	uM
methyl N-[3-(2-acetamidoethyl)-1H-indol-5-yl]carbamate	594262: Binding affinity to low affinity melatonin (MT3) site of quinone reductase 2	ic50	0.0027	uM
N-[2-(5-methoxy-1-methylindol-3-yl)ethyl]acetamide	107724: Inhibition of 2-[125I]iodomelatonin binding to Melatonin receptor 3 (MT3) of Syrian hamster brain membrane	ki	0.0028	uM
ethyl 3-(2-acetamidoethyl)-5-methoxy-1H-indole-2-carboxylate	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0030	uM
Pacritinib	1425093: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0040	uM
11-amino-10-chloro-2-methyl-9-(methylamino)-3-oxo-2,7-diazatricyclo[6.3.1.04,12]dodeca-1(11),4,6,8(12),9-pentaene-6-carboxamide	643961: Inhibition of human quinone reductase 2 using NMeH as substrate by MTT assay	ic50	0.0041	uM
N-[2-[7-(methylsulfamoyl)naphthalen-1-yl]ethyl]acetamide	594258: Binding affinity to human low affinity melatonin (MT3) site of quinone reductase 2	ic50	0.0049	uM
10-[2-(diethylamino)ethylamino]-8-hydroxy-4,5-dimethoxy-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2,4,7,9,11,13(16),14-heptaen-6-one	479979: Inhibition of human recombinant NQO2 assessed as reduction of DCPIP by spectrophotometry	ic50	0.0060	uM
N-[2-(2-iodo-5-methoxy-1-methyl-6-nitroindol-3-yl)ethyl]acetamide	107724: Inhibition of 2-[125I]iodomelatonin binding to Melatonin receptor 3 (MT3) of Syrian hamster brain membrane	ki	0.0061	uM
N-[2-(2-iodo-5-methoxy-1H-indol-3-yl)ethyl]acetamide	107724: Inhibition of 2-[125I]iodomelatonin binding to Melatonin receptor 3 (MT3) of Syrian hamster brain membrane	ki	0.0065	uM
N-[2-(7-hydroxynaphthalen-1-yl)ethyl]but-3-enamide	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0078	uM
Prazosin	594262: Binding affinity to low affinity melatonin (MT3) site of quinone reductase 2	ic50	0.0078	uM
10-[2-(diethylamino)ethylamino]-5-methoxy-15-methyl-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2(7),3,5,9,11,13(16),14-heptaen-8-one	479979: Inhibition of human recombinant NQO2 assessed as reduction of DCPIP by spectrophotometry	ic50	0.0090	uM
2,2,2-trifluoro-N-[2-(6-methoxy-3H-inden-1-yl)ethyl]acetamide	107722: Ability to inhibit 2-[125I]iodomelatonin specific binding to melatonin receptor 3 (MT3) of Syrian hamster brain.	ki	0.0091	uM
N-[2-[7-(methylsulfamoyl)naphthalen-1-yl]ethyl]furan-2-carboxamide	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0091	uM
6-methoxy-2-methyl-N-[(E)-pyridin-3-ylmethylideneamino]quinolin-4-amine	1566052: Inhibition of recombinant human NQO2 expressed in Escherichia coli using DCPIP as substrate by spectrophotometry	ic50	0.0100	uM
N-[2-(7-hydroxynaphthalen-1-yl)ethyl]furan-2-carboxamide	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0110	uM
methyl N-[3-[2-(but-3-enoylamino)ethyl]-1-benzofuran-5-yl]carbamate	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0110	uM
8-(acetamidomethyl)-N-methylnaphthalene-2-carboxamide	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0120	uM
2-methoxy-6-[(E)-[(6-methoxy-2-methylquinolin-4-yl)hydrazinylidene]methyl]phenol	1566052: Inhibition of recombinant human NQO2 expressed in Escherichia coli using DCPIP as substrate by spectrophotometry	ic50	0.0130	uM
2-[(5-methoxy-8-oxo-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2(7),3,5,9,11,13(16),14-heptaen-10-yl)amino]-N,N-dimethylethanamine oxide	621612: Inhibition of human recombinant NQO2 assessed as reduction of DCPIP by spectrophotometry	ic50	0.0140	uM
methyl 3-(2-acetamidoethyl)-1-benzofuran-5-carboxylate	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0141	uM
3-[2-(7-methoxynaphthalen-1-yl)ethyl]-1,3-oxazolidin-2-one	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0141	uM
acetic acid;4-[5-(3-nitrophenyl)furan-2-yl]benzenecarboximidamide	1281396: Inhibition of human recombinant NQO2 using DCPIPas substrate and NRH as cofactor measured for 1 min by spectrophotometry in the absence of BSA	ic50	0.0145	uM
6-methoxy-2-methyl-N-[(E)-2-phenylethylideneamino]quinolin-4-amine	1566052: Inhibition of recombinant human NQO2 expressed in Escherichia coli using DCPIP as substrate by spectrophotometry	ic50	0.0150	uM
acetic acid;4-[5-(4-nitrophenyl)furan-2-yl]benzenecarboximidamide	1281396: Inhibition of human recombinant NQO2 using DCPIPas substrate and NRH as cofactor measured for 1 min by spectrophotometry in the absence of BSA	ic50	0.0152	uM
methyl N-[3-(2-acetamidoethyl)-1-benzofuran-5-yl]carbamate	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0158	uM
10-[2-(diethylamino)ethylamino]-5-hydroxy-15-methyl-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2(7),3,5,9,11,13(16),14-heptaen-8-one	479979: Inhibition of human recombinant NQO2 assessed as reduction of DCPIP by spectrophotometry	ic50	0.0160	uM
10-[2-(diethylamino)ethylamino]-3,6-dimethoxy-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2,4,6,9,11,13(16),14-heptaen-8-one	479979: Inhibition of human recombinant NQO2 assessed as reduction of DCPIP by spectrophotometry	ic50	0.0170	uM
6-methoxy-2-methyl-N-[(E)-(5-nitrofuran-2-yl)methylideneamino]quinolin-4-amine	1566052: Inhibition of recombinant human NQO2 expressed in Escherichia coli using DCPIP as substrate by spectrophotometry	ic50	0.0180	uM
N-[2-(7-methylsulfanylnaphthalen-1-yl)ethyl]acetamide	594258: Binding affinity to human low affinity melatonin (MT3) site of quinone reductase 2	ic50	0.0180	uM
4,5,6,7-tetrabromo-1H-benzimidazole	1801064: Fluorescence Titration Assay from Article 10.1021/bi500959t: “Quinone reductase 2 is an adventitious target of protein kinase CK2 inhibitors TBBz (TBI) and DMAT.”	kd	0.0181	uM
methyl 3-[2-(cyclopentanecarbonylamino)ethyl]-1-benzofuran-5-carboxylate	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0182	uM
N-[2-(7-methylsulfonylnaphthalen-1-yl)ethyl]acetamide	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0209	uM
methyl N-[3-[2-(2-methylpropanoylamino)ethyl]-1-benzofuran-5-yl]carbamate	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0229	uM
methyl N-[8-[(cyclopropanecarbonylamino)methyl]naphthalen-2-yl]carbamate	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0240	uM
acetic acid;4-[5-(4-bromophenyl)furan-2-yl]benzenecarboximidamide	1281396: Inhibition of human recombinant NQO2 using DCPIPas substrate and NRH as cofactor measured for 1 min by spectrophotometry in the absence of BSA	ic50	0.0270	uM
Melatonin	107722: Ability to inhibit 2-[125I]iodomelatonin specific binding to melatonin receptor 3 (MT3) of Syrian hamster brain.	ki	0.0276	uM
N-(2-naphthalen-1-ylethyl)methanesulfonamide	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0282	uM
N-[2-(7-methoxynaphthalen-1-yl)ethyl]benzamide	396398: Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	ic50	0.0288	uM
10-[2-(diethylamino)ethylamino]-8-hydroxy-3-methoxy-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2,4,7,9,11,13(16),14-heptaen-6-one	479979: Inhibition of human recombinant NQO2 assessed as reduction of DCPIP by spectrophotometry	ic50	0.0310	uM
N-[2-(7-sulfamoylnaphthalen-1-yl)ethyl]acetamide	594258: Binding affinity to human low affinity melatonin (MT3) site of quinone reductase 2	ic50	0.0320	uM
4-[5-(4-carbamimidoylphenyl)furan-2-yl]benzenecarboximidamide	1391153: Inhibition of recombinant human NQO2 assessed as change in rate of decolouration of DCPIP measured over 1 min by spectrophotometric method	ic50	0.0350	uM
acetic acid;4-[5-(4-carbamimidoylphenyl)furan-2-yl]benzenecarboximidamide	1281396: Inhibition of human recombinant NQO2 using DCPIPas substrate and NRH as cofactor measured for 1 min by spectrophotometry in the absence of BSA	ic50	0.0350	uM

CTD chemical–gene interactions

96 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects binding, increases oxidation, increases reduction, affects localization, affects cotreatment (+5 more)	9
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
sodium arsenite	increases expression	5
Cyclosporine	affects cotreatment, increases expression, decreases expression	4
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	3
Clozapine	increases expression, affects response to substance, decreases reaction, increases reduction, increases activity	3
Quercetin	affects binding, decreases reaction, increases reduction, decreases expression	3
Tetrachlorodibenzodioxin	increases expression	3
bisphenol A	increases expression	2
trichostatin A	affects expression, increases expression	2
sulforaphane	increases expression	2
nicotinamide-beta-riboside	increases oxidation, increases reduction, decreases reaction	2
entinostat	increases expression, affects cotreatment	2
N-(2-(2-methoxy-6H-dipyrido(2,3-a-3,2-e)pyrrolizin-11-yl)ethyl)-2-furamide	increases oxidation, increases reduction, increases activity, decreases activity, decreases reaction	2
Panobinostat	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Melatonin	affects activity, decreases reaction, increases oxidation, increases reduction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Zinc	affects cotreatment, increases expression, affects expression	2
2,6-Dichloroindophenol	increases oxidation, increases reduction, decreases reaction	2
Aflatoxin B1	affects expression, increases methylation	2
Vitamin K 3	increases reduction, increases oxidation, decreases reaction	2
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
chrysoeriol	decreases reaction, increases oxidation, increases reduction	1
hesperetin	affects binding	1
beta-lapachone	increases expression	1

ChEMBL screening assays

93 unique, capped per target: 93 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1016924	Binding	Displacement of [125I]iodomelatonin from MT3/QR2 melatonin binding site expressed in CHO cells	A novel quantitative structure-activity relationship method to predict the affinities of MT3 melatonin binding site. — Eur J Med Chem

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1PD	Abcam K-562 NQO2 KO	Cancer cell line	Female
CVCL_D2KZ	Abcam Raji NQO2 KO	Cancer cell line	Male
CVCL_D8RM	Ubigene HCT 116 NQO2 KO	Cancer cell line	Male
CVCL_E1KG	HyCyte HEK293T KO-hNQO2	Transformed cell line	Female
CVCL_TA99	HAP1 NQO2 (-) 1	Cancer cell line	Male
CVCL_WQ16	Abcam Jurkat NQO2 KO	Cancer cell line	Male
CVCL_XR07	HAP1 NQO2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	PHASE3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	PHASE3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	PHASE3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer