ES-936

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H16N2O6
Molecular Weight	356.3294
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(=O)C2=C(C(COC3=CC=C(C=C3)[N+]([O-])=O)=C(C)N2C)C1=O

InChI

InChIKey=IBLWSLZYYZHSRG-UHFFFAOYSA-N

InChI=1S/C18H16N2O6/c1-10-13(9-26-12-6-4-11(5-7-12)20(23)24)16-17(19(10)2)14(21)8-15(25-3)18(16)22/h4-8H,9H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C18H16N2O6
Molecular Weight	356.3294
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20433816 | https://www.ncbi.nlm.nih.gov/pubmed/19364812

ES936 is a potent mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1), that exhibited potent growth inhibition effects against human pancreatic cancer cell lines. It was also shown, that drug can stimulate DNA synthesis in some cells through a mechanism involving p38 MAPK.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
NAD(P)H dehydrogenase [quinone] 1 1 Target ID: P15559 Gene ID: 1728.0 Gene Symbol: NQO1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12920209	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2596

PubMed

Title	Date	PubMed
Role for NAD(P)H:quinone oxidoreductase 1 and manganese-dependent superoxide dismutase in 17-(allylamino)-17-demethoxygeldanamycin-induced heat shock protein 90 inhibition in pancreatic cancer cells.	2011-03	21156818
ES936 stimulates DNA synthesis in HeLa cells independently on NAD(P)H:quinone oxidoreductase 1 inhibition, through a mechanism involving p38 MAPK.	2010-07-30	20433816
NAD(P)H:quinone oxidoreductase 1-compromised human bone marrow endothelial cells exhibit decreased adhesion molecule expression and CD34+ hematopoietic cell adhesion.	2010-07	20378716
Development of indolequinone mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1): NQO1 inhibition and growth inhibitory activity in human pancreatic MIA PaCa-2 cancer cells.	2007-05-22	17455910
Role of NAD(P)H:quinone oxidoreductase 1 in clofibrate-mediated hepatoprotection from acetaminophen.	2007-02-12	17188792
The highly expressed and inducible endogenous NAD(P)H:quinone oxidoreductase 1 in cardiovascular cells acts as a potential superoxide scavenger.	2007	17901563
The bioreduction of a series of benzoquinone ansamycins by NAD(P)H:quinone oxidoreductase 1 to more potent heat shock protein 90 inhibitors, the hydroquinone ansamycins.	2006-10	16825487
5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1, exhibits activity against human pancreatic cancer in vitro and in vivo.	2006-07	16891456
The crystal structure of NAD(P)H quinone oxidoreductase 1 in complex with its potent inhibitor dicoumarol.	2006-05-23	16700548
Formation of 17-allylamino-demethoxygeldanamycin (17-AAG) hydroquinone by NAD(P)H:quinone oxidoreductase 1: role of 17-AAG hydroquinone in heat shock protein 90 inhibition.	2005-11-01	16267026
Dicoumarol relieves serum withdrawal-induced G0/1 blockade in HL-60 cells through a superoxide-dependent mechanism.	2005-06-01	15896341
RH1 induces cellular damage in an NAD(P)H:quinone oxidoreductase 1-dependent manner: relationship between DNA cross-linking, cell cycle perturbations, and apoptosis.	2005-05	15665137
NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger.	2004-05	15102952
Biochemical, cytotoxic, and genotoxic effects of ES936, a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1, in cellular systems.	2003-09	12920209
Kinetics of NAD(P)H:quinone oxidoreductase I (NQO1) inhibition by mitomycin C in vitro and in vivo.	2003-06	12649308
Characterization of a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 by biochemical, X-ray crystallographic, and mass spectrometric approaches.	2001-12-18	11735396

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

ES936 (100 nM) inhibits more than 95% of NAD(P)H:quinone oxidoreductase 1 (NQO1) activity within 30 min and is stable in complete media at this concentration for a minimum of 2 h. The duration of inhibition is cell line-specific because a new protein must be generated for resumption of activity. ES936 abrogates the toxicity of streptonigrin, with greater effects seen in cell lines expressing higher levels of NQO1. ES936 does not inhibit other cellular reductases, nor does it alter cellular levels of acid-soluble thiols. Some evidence of DNA strand breaks was observed at the concentrations of ES936 required for the inhibition of NQO1 activity. It was proposed the use of ES936 (100 nM) as a mechanism-based inhibitor of NQO1 in cellular systems and for use as a component of the routine activity assay for NQO1.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 23:36:11 GMT 2025` Edited by `admin` on `Mon Mar 31 23:36:11 GMT 2025`
Record UNII	1XI90I177M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ES-936

Common Name

English

1H-INDOLE-4,7-DIONE, 5-METHOXY-1,2-DIMETHYL-3-((4-NITROPHENOXY)METHYL)-

Preferred Name

English

Code System Code Type Description

PUBCHEM

4470790