Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8XK6L)

• DTT 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
• Gene Name: NQO1
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Choreiform disorder [ICD-11: 8A01]
  CNS anomalies syndrome [ICD-11: LD20]
  Inborn energy metabolism error [ICD-11: 5C53]
  Intellectual development disorder [ICD-11: LD90]
  Pancreatic cancer [ICD-11: 2C10]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• BioChemical Class: NADH/NADPH oxidoreductase
• UniProt ID: NQO1_HUMAN
• TTD ID: T52389
• EC Number: EC 1.6.5.2
• Sequence:
  MVGRRALIVLAHSERTSFNYAMKEAAAAALKKKGWEVVESDLYAMNFNPIISRKDITGKL
  KDPANFQYPAESVLAYKEGHLSPDIVAEQKKLEAADLVIFQFPLQWFGVPAILKGWFERV
  FIGEFAYTYAAMYDKGPFRSKKAVLSITTGGSGSMYSLQGIHGDMNVILWPIQSGILHFC
  GFQVLEPQLTYSIGHTPADARIQILEGWKKRLENIWDETPLYFAPSSLFDLNFQAGFLMK
  KEVQDEEKNKKFGLSVGHHLGKSIPTDNQIKARK
• 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.
• Reactome Pathway:
  Nuclear events mediated by NFE2L2 (R-HSA-9759194)
  Regulation of ornithine decarboxylase (ODC) (R-HSA-350562)
• BioCyc Pathway: MetaCyc:HS11566-MON

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARQ 761	DMH5CAL	Pancreatic cancer	2C10	Phase 2	[2]
BioE-743	DM7PT8R	Leigh syndrome	5C53.24	Phase 2	[3]
Coenzyme Q10 analog	DMO0VGH	Huntington disease	8A01.10	Phase 2	[1]

28 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-Benzyl-1-hydroxy-3H-benzo[f]chromen-3-one	DMV7IWE	Discovery agent	N.A.	Investigative	[4]
3-(3,4-Dimethylbenzyl)-4-hydroxy-2H-chromen-2-one	DM9BYVL	Discovery agent	N.A.	Investigative	[4]
3-Benzyl-4-hydroxy-2H-benzo[h]chromen-2-one	DMA5EHC	Discovery agent	N.A.	Investigative	[4]
3-Benzyl-4-hydroxy-2H-chromen-2-one	DM3BFX0	Discovery agent	N.A.	Investigative	[4]
3-Benzyl-4-hydroxy-6,7-dimethyl-2H-chromen-2-one	DML0ME9	Discovery agent	N.A.	Investigative	[4]
4-amino-2H-chromen-2-one	DM3MUF1	Discovery agent	N.A.	Investigative	[5]
4-Hydroxy-3-(1-naphthylmethyl)-2H-chromen-2-one	DMY3OHK	Discovery agent	N.A.	Investigative	[4]
4-Hydroxy-3-(2-naphthylmethyl)-2H-chromen-2-one	DMM3QPL	Discovery agent	N.A.	Investigative	[4]
Bishydroxy[2h-1-Benzopyran-2-One,1,2-Benzopyrone]	DMVRXH3	Discovery agent	N.A.	Investigative	[6]
Duroquinone	DML7YPS	Discovery agent	N.A.	Investigative	[6]
ES-936	DMIVZ3W	Discovery agent	N.A.	Investigative	[7]
Ethyl Bis(4-hydroxy-2-oxo-2H-chromen-3-yl)acetate	DMJQTIK	Discovery agent	N.A.	Investigative	[4]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[6]
NSC-106080	DMR6P9S	Discovery agent	N.A.	Investigative	[8]
NSC-106547	DMR2DTI	Discovery agent	N.A.	Investigative	[9]
NSC-2113	DMOGV9F	Discovery agent	N.A.	Investigative	[9]
NSC-224124	DMM9PDR	Discovery agent	N.A.	Investigative	[9]
NSC-275420	DMV2D8F	Discovery agent	N.A.	Investigative	[9]
NSC-316158	DMTPRXI	Discovery agent	N.A.	Investigative	[9]
NSC-339580	DMK0H2P	Discovery agent	N.A.	Investigative	[9]
NSC-339583	DMITE1A	Discovery agent	N.A.	Investigative	[9]
NSC-354279	DMVL51I	Discovery agent	N.A.	Investigative	[9]
NSC-621351	DMFXEIK	Discovery agent	N.A.	Investigative	[8]
NSC-645808	DMMBAR3	Discovery agent	N.A.	Investigative	[9]
NSC-645827	DMNJLW2	Discovery agent	N.A.	Investigative	[9]
NSC-65069	DMFEGYB	Discovery agent	N.A.	Investigative	[8]
NSC-73410	DMX0VQN	Discovery agent	N.A.	Investigative	[9]
NSC-99528	DMXZAIG	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Bladder cancer	2C82	Bladder tissue	2.05E-04	0.89	2.67

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Quinone reductase 1 (NQO1) DME Info
• Gene Name: NQO1

4 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carboplatin	DMG281S	Ovarian cancer	2C73	Approved	[10]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[10]
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[11]
Oxaliplatin	DMQNWRD	Colorectal cancer	2B91.Z	Approved	[10]

1 Clinical Trial Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Beta-lapachone	DMMI84K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]

1 Discontinued Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CB1954	DMVP4YK	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[13]

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitrobenzanthrone	DMN6L70	Discovery agent	N.A.	Investigative	[14]

References

• [1] Therapeutic strategies for Leber's hereditary optic neuropathy: A current update. Intractable Rare Dis Res. 2013 November; 2(4): 130-135.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] 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.
• [5] 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.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] 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.
• [8] 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.
• [9] In silico identification and biochemical characterization of novel inhibitors of NQO1. Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54.
• [10] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
• [11] Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52.
• [12] Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice. PLoS One. 2012;7(10):e47122.
• [13] Gene Therapy of the Central Nervous System. Charter 22 - Prodrug-Activation Gene Therapy. 2006, Pages 291-301
• [14] Dose-dependent response to 3-nitrobenzanthrone exposure in human urothelial cancer cells. Chem Res Toxicol. 2017 Oct 16;30(10):1855-1864.