Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMIVZ3W)

• Drug Name: ES-936 Drug Info
• Synonyms: 192820-78-3; ES 936; UNII-1XI90I177M; 5-METHOXY-1,2-DIMETHYL-3-(4-NITROPHENOXYMETHYL)INDOLE-4,7-DIONE; 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione; 1XI90I177M; 5-methoxy-1,2-dimethyl-3-((4-nitrophenoxy)methyl)indole-4,7-dione; AC1NBNHW; CHEMBL357217; SCHEMBL3991028; CTK8E6509; DTXSID20172879; MolPort-006-168-362; ZINC587989; AKOS024457934; 1H-Indole-4,7-dione, 5-methoxy-1,2-dimethyl-3-((4-nitrophenoxy)methyl)-; API0010300; DB02400; ES936, > LS-191843; B5514; KS-00000189; J-012477

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 4470790
  CAS Number: CAS 192820-78-3
  TTD Drug ID: DMIVZ3W

Molecule-Related Drug Atlas

Drug(s) Targeting Quinone reductase 1 (NQO1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARQ 761	DMH5CAL	Pancreatic cancer	2C10	Phase 2	[3]
Coenzyme Q10 analog	DMO0VGH	Huntington disease	8A01.10	Phase 2	[4]
BioE-743	DM7PT8R	Leigh syndrome	5C53.24	Phase 2	[5]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[6]
NSC-645808	DMMBAR3	Discovery agent	N.A.	Investigative	[7]
NSC-106080	DMR6P9S	Discovery agent	N.A.	Investigative	[8]
NSC-99528	DMXZAIG	Discovery agent	N.A.	Investigative	[8]
NSC-354279	DMVL51I	Discovery agent	N.A.	Investigative	[7]
Duroquinone	DML7YPS	Discovery agent	N.A.	Investigative	[6]
Ethyl Bis(4-hydroxy-2-oxo-2H-chromen-3-yl)acetate	DMJQTIK	Discovery agent	N.A.	Investigative	[9]

Drug(s) Affected By NAD(P)H dehydrogenase 1 (NQO1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[10]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[11]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[12]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[13]
TECFIDERA	DM2OVDT	Multiple sclerosis	8A40	Approved	[14]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[15]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[16]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Quinone reductase 1 (NQO1)	TT8XK6L	NQO1_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Gene/Protein Processing	[2]

References

• [1] 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.
• [2] Dicoumarol relieves serum withdrawal-induced G0/1 blockade in HL-60 cells through a superoxide-dependent mechanism. Biochem Pharmacol. 2005 Jun 1;69(11):1613-25.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Therapeutic strategies for Leber's hereditary optic neuropathy: A current update. Intractable Rare Dis Res. 2013 November; 2(4): 130-135.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] In silico identification and biochemical characterization of novel inhibitors of NQO1. Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54.
• [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] 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.
• [10] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [11] Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes. Arch Toxicol. 2018 Jan;92(1):371-381.
• [12] Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321. doi: 10.1016/j.redox.2019.101321. Epub 2019 Sep 5.
• [13] Gypenosides protect retinal pigment epithelium cells from oxidative stress. Food Chem Toxicol. 2018 Feb;112:76-85.
• [14] Enhanced cytotoxicity of bioreductive antitumor agents with dimethyl fumarate in human glioblastoma cells. Anticancer Drugs. 2005 Feb;16(2):167-74.
• [15] Growth-suppressive effect of non-steroidal anti-inflammatory drugs on 11 colon-cancer cell lines and fluorescence differential display of genes whose expression is influenced by sulindac. Int J Cancer. 2000 Dec 15;88(6):873-80. doi: 10.1002/1097-0215(20001215)88:6<873::aid-ijc6>3.0.co;2-b.
• [16] Simvastatin protects dopaminergic neurons against MPP+-induced oxidative stress and regulates the endogenous anti-oxidant system through ERK. Cell Physiol Biochem. 2018;51(4):1957-1968.
• [17] P450 3A-catalyzed O-dealkylation of lapatinib induces mitochondrial stress and activates Nrf2. Chem Res Toxicol. 2016 May 16;29(5):784-96.
• [18] Induction of human NAD(P)H:quinone oxidoreductase (NQO1) gene expression by the flavonol quercetin. Toxicol Lett. 2001 Feb 3;119(1):49-57.
• [19] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.