PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
21718050-7	2011	Computation-based molecular modeling simulations demonstrated favorable conformations of indolequinones positioned directly above and in parallel with the isoalloxazine ring of FAD, and mass spectrometry extended our previous finding of adduction of the FAD in the active site of NQO2 by an indolequinone-derived iminium electrophile to the wider series of indolequinone inhibitors.	Indolequinones	291-304	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	280-284
22147753-0	2012	Antitumor indolequinones induced apoptosis in human pancreatic cancer cells via inhibition of thioredoxin reductase and activation of redox signaling.	Indolequinones	10-24	peroxiredoxin 5	Homo sapiens	94-115
21718050-0	2011	Indolequinone inhibitors of NRH:quinone oxidoreductase 2.	Indolequinones	0-13	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	28-56
21718050-2	2011	We describe a series of indolequinones as efficient mechanism-based inhibitors of NRH:quinone oxidoreductase 2 (NQO2) for use either in cellular or cell-free systems.	Indolequinones	24-38	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	82-110
21718050-10	2011	These indolequinones were irreversible inhibitors and were found to be at least 1 order of magnitude more potent than any previously documented competitive inhibitors of NQO2 and represent the first mechanism-based inhibitors of NQO2 to be characterized in cellular systems.	Indolequinones	6-20	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	170-174
21718050-2	2011	We describe a series of indolequinones as efficient mechanism-based inhibitors of NRH:quinone oxidoreductase 2 (NQO2) for use either in cellular or cell-free systems.	Indolequinones	24-38	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	112-116
21718050-5	2011	Inhibition of recombinant human NQO2 by the indolequinones was NRH-dependent, with kinetic parameters characteristic of mechanism-based inhibition and partition ratios as low as 2.0.	Indolequinones	44-58	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	32-36
21718050-10	2011	These indolequinones were irreversible inhibitors and were found to be at least 1 order of magnitude more potent than any previously documented competitive inhibitors of NQO2 and represent the first mechanism-based inhibitors of NQO2 to be characterized in cellular systems.	Indolequinones	6-20	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	229-233
21718050-6	2011	Indolequinones inhibited NQO2 activity in K562 cells at nanomolar concentrations that did not inhibit NQO1 and were nontoxic to cells.	Indolequinones	0-14	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	25-29
20433816-1	2010	The indolequinone ES936 (5-methoxy-1,2-dimethyl-3-[(4-nitrophenol)methyl]-indole-4,7-dione) is a potent mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1).	Indolequinones	4-17	NAD(P)H quinone dehydrogenase 1	Homo sapiens	133-165
21718050-7	2011	Computation-based molecular modeling simulations demonstrated favorable conformations of indolequinones positioned directly above and in parallel with the isoalloxazine ring of FAD, and mass spectrometry extended our previous finding of adduction of the FAD in the active site of NQO2 by an indolequinone-derived iminium electrophile to the wider series of indolequinone inhibitors.	Indolequinones	89-103	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	280-284
21718050-7	2011	Computation-based molecular modeling simulations demonstrated favorable conformations of indolequinones positioned directly above and in parallel with the isoalloxazine ring of FAD, and mass spectrometry extended our previous finding of adduction of the FAD in the active site of NQO2 by an indolequinone-derived iminium electrophile to the wider series of indolequinone inhibitors.	Indolequinones	89-102	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	280-284
21506232-2	2011	In order to explore the potential of NQO2 as a therapeutic target, we have developed potent and selective mechanism-based inhibitors centered on the indolequinone pharmacophore.	Indolequinones	149-162	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	37-41
21506232-5	2011	These indolequinones represent the first mechanism-based inhibitors of NQO2, and their novel mode of action involving alkylation of the flavin cofactor, provides significant advantages over existing competitive inhibitors in terms of potency and irreversibility, and will open new opportunities to define the role of NQO2 in disease.	Indolequinones	6-20	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	71-75
21506232-5	2011	These indolequinones represent the first mechanism-based inhibitors of NQO2, and their novel mode of action involving alkylation of the flavin cofactor, provides significant advantages over existing competitive inhibitors in terms of potency and irreversibility, and will open new opportunities to define the role of NQO2 in disease.	Indolequinones	6-20	N-ribosyldihydronicotinamide:quinone reductase 2	Homo sapiens	317-321
21168332-0	2011	(13)C-labeled indolequinone-DTPA-Gd conjugate for NMR probing cytochrome:P450 reductase-mediated one-electron reduction.	Indolequinones	14-27	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	62-77
20433816-1	2010	The indolequinone ES936 (5-methoxy-1,2-dimethyl-3-[(4-nitrophenol)methyl]-indole-4,7-dione) is a potent mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1).	Indolequinones	4-17	NAD(P)H quinone dehydrogenase 1	Homo sapiens	167-171
17455910-0	2007	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.	Indolequinones	15-28	NAD(P)H quinone dehydrogenase 1	Homo sapiens	59-91
19364812-0	2009	Potent activity of indolequinones against human pancreatic cancer: identification of thioredoxin reductase as a potential target.	Indolequinones	19-33	peroxiredoxin 5	Homo sapiens	85-106
19364812-6	2009	A potential target of these indolequinones was identified as thioredoxin reductase.	Indolequinones	28-42	peroxiredoxin 5	Homo sapiens	61-82
19364812-7	2009	Indolequinones were found to be potent inhibitors of thioredoxin reductase activity both in pancreatic cancer cells and in cell-free systems.	Indolequinones	0-14	peroxiredoxin 5	Homo sapiens	53-74
19364812-8	2009	The mechanism of action of the indolequinones was shown to involve metabolic reduction, loss of a leaving group to generate a reactive electrophile resulting in alkylation of the selenocysteine residue in the active site of thioredoxin reductase.	Indolequinones	31-45	peroxiredoxin 5	Homo sapiens	224-245
19364812-10	2009	Inhibition of thioredoxin reductase represents a potential novel target in pancreatic cancer and may provide a biomarker of effect of lead indolequinones in this type of cancer.	Indolequinones	139-153	peroxiredoxin 5	Homo sapiens	14-35
17944451-3	2007	The ability of these indolequinones to function as mechanism-based inhibitors of purified recombinant human NQO1 was evaluated, as was their ability to inhibit both NQO1 and cell growth in human pancreatic MIA PaCa-2 tumor cells.	Indolequinones	21-35	NAD(P)H quinone dehydrogenase 1	Homo sapiens	165-169
17944451-3	2007	The ability of these indolequinones to function as mechanism-based inhibitors of purified recombinant human NQO1 was evaluated, as was their ability to inhibit both NQO1 and cell growth in human pancreatic MIA PaCa-2 tumor cells.	Indolequinones	21-35	NAD(P)H quinone dehydrogenase 1	Homo sapiens	108-112
17455910-0	2007	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.	Indolequinones	15-28	NAD(P)H quinone dehydrogenase 1	Homo sapiens	93-97
17571194-2	2007	The ability of these indolequinones to act as substrates for recombinant human NAD(P)H:quinone oxidoreductase (NQO1), a two-electron reductase upregulated in tumour cells, was determined, along with their toxicity to an isogenic tumour cell line pair that is differentiated as either NQO1-expressing cells (BE-NQ) or NQO1-null cells (BE-WT).	Indolequinones	21-35	NAD(P)H quinone dehydrogenase 1	Homo sapiens	111-115
17571194-2	2007	The ability of these indolequinones to act as substrates for recombinant human NAD(P)H:quinone oxidoreductase (NQO1), a two-electron reductase upregulated in tumour cells, was determined, along with their toxicity to an isogenic tumour cell line pair that is differentiated as either NQO1-expressing cells (BE-NQ) or NQO1-null cells (BE-WT).	Indolequinones	21-35	NAD(P)H quinone dehydrogenase 1	Homo sapiens	284-288
17571194-2	2007	The ability of these indolequinones to act as substrates for recombinant human NAD(P)H:quinone oxidoreductase (NQO1), a two-electron reductase upregulated in tumour cells, was determined, along with their toxicity to an isogenic tumour cell line pair that is differentiated as either NQO1-expressing cells (BE-NQ) or NQO1-null cells (BE-WT).	Indolequinones	21-35	NAD(P)H quinone dehydrogenase 1	Homo sapiens	284-288
17455910-0	2007	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.	Indolequinones	15-28	NAD(P)H quinone dehydrogenase 1	Homo sapiens	100-104
17455910-2	2007	In this report, we describe a series of indolequinones, based on 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), and evaluate NQO1 inhibition and growth inhibitory activity in the human pancreatic MIA PaCa-2 tumor cell line.	Indolequinones	40-54	NAD(P)H quinone dehydrogenase 1	Homo sapiens	153-157
17455910-3	2007	The indolequinones with 4-nitrophenoxy, 4-pyridinyloxy, and acetoxy substituents at the (indol-3-yl)methyl position were NADH-dependent inhibitors of recombinant human NQO1, indicative of mechanism-based inhibition.	Indolequinones	4-18	NAD(P)H quinone dehydrogenase 1	Homo sapiens	168-172
17455910-5	2007	The ability of this series of indolequinones to inhibit recombinant human NQO1 correlated with NQO1 inhibition in MIA PaCa-2 cells.	Indolequinones	30-44	NAD(P)H quinone dehydrogenase 1	Homo sapiens	74-78
17455910-5	2007	The ability of this series of indolequinones to inhibit recombinant human NQO1 correlated with NQO1 inhibition in MIA PaCa-2 cells.	Indolequinones	30-44	NAD(P)H quinone dehydrogenase 1	Homo sapiens	95-99
17455910-5	2007	The ability of this series of indolequinones to inhibit recombinant human NQO1 correlated with NQO1 inhibition in MIA PaCa-2 cells.	Indolequinones	30-44	MIA SH3 domain containing	Homo sapiens	114-117
17455910-6	2007	The examination of indolequinone interactions in complex with NQO1 from computational-based molecular docking simulations supported the observed biochemical data with respect to NQO1 inhibition.	Indolequinones	19-32	NAD(P)H quinone dehydrogenase 1	Homo sapiens	62-66
17455910-6	2007	The examination of indolequinone interactions in complex with NQO1 from computational-based molecular docking simulations supported the observed biochemical data with respect to NQO1 inhibition.	Indolequinones	19-32	NAD(P)H quinone dehydrogenase 1	Homo sapiens	178-182
17455910-10	2007	These data demonstrate that NQO1 inhibitory activity can be dissociated from growth inhibitory activity and suggest additional or alternative targets to NQO1 that are responsible for the growth inhibitory activity of this series of indolequinones in human pancreatic cancer.	Indolequinones	232-246	NAD(P)H quinone dehydrogenase 1	Homo sapiens	28-32
17455910-10	2007	These data demonstrate that NQO1 inhibitory activity can be dissociated from growth inhibitory activity and suggest additional or alternative targets to NQO1 that are responsible for the growth inhibitory activity of this series of indolequinones in human pancreatic cancer.	Indolequinones	232-246	NAD(P)H quinone dehydrogenase 1	Homo sapiens	153-157
15498501-1	2004	The indolequinone compound EO9 has good pharmacodynamic properties in terms of bioreductive activation and selectivity for either NAD(P)H:quinone oxidoreductase-1 (NQO1)-rich aerobic or NQO1-deficient hypoxic cells.	Indolequinones	4-17	NAD(P)H dehydrogenase, quinone 1	Mus musculus	130-162
17388633-6	2007	The reactivity of indolequinones 2 and 3 is further decreased due to their stronger electron-donating substituents at C-4.	Indolequinones	18-32	complement C4A (Rodgers blood group)	Homo sapiens	118-121
15498501-1	2004	The indolequinone compound EO9 has good pharmacodynamic properties in terms of bioreductive activation and selectivity for either NAD(P)H:quinone oxidoreductase-1 (NQO1)-rich aerobic or NQO1-deficient hypoxic cells.	Indolequinones	4-17	NAD(P)H dehydrogenase, quinone 1	Mus musculus	164-168
14505799-5	2003	The C-3 and C-5 positions of the indolequinone nucleus were modified to manipulate reactivity of the reduction products and the four prodrugs were identified as NQO1 substrates of varying specificity.	Indolequinones	33-46	complement C3	Homo sapiens	4-15
14505799-5	2003	The C-3 and C-5 positions of the indolequinone nucleus were modified to manipulate reactivity of the reduction products and the four prodrugs were identified as NQO1 substrates of varying specificity.	Indolequinones	33-46	NAD(P)H quinone dehydrogenase 1	Homo sapiens	161-165
14505799-12	2003	This study identifies a candidate indolequinone analogue for further development as a dual hypoxia and NQO1-directed prodrug.	Indolequinones	34-47	NAD(P)H quinone dehydrogenase 1	Homo sapiens	103-107
11735396-4	2001	The orientation of ES936 in the active site of NQO1 was examined by X-ray crystallography and found to be opposite to that observed for other indolequinones acting as substrates.	Indolequinones	142-156	NAD(P)H quinone dehydrogenase 1	Homo sapiens	47-51
10910079-6	2000	Based on sulforhodamine B assays for the number of viable cells, the NQO1 clones showed increased sensitivity to EO9, an indoloquinone that undergoes bioactive reduction by NQO1.	Indolequinones	121-134	NAD(P)H quinone dehydrogenase 1	Homo sapiens	69-73
11040064-8	2000	Functional validation of the isogenic model was provided by the much greater sensitivity of the NQO1-transfected cells to the known DT-diaphorase substrates and bioreductive agents streptonigrin (113- to 132-fold) and indoloquinone EO9 (17- to 25-fold) and the inhibition of this potentiation by the DT-diaphorase inhibitor dicoumarol.	Indolequinones	218-231	NAD(P)H quinone dehydrogenase 1	Homo sapiens	96-100
11448456-1	2001	Evidence suggests that DT-diaphorase is involved in the activation and mechanism of cytotoxicity of the investigational indoloquinone anticancer drug EO9 under aerobic conditions.	Indolequinones	120-133	NAD(P)H quinone dehydrogenase 1	Rattus norvegicus	23-36
10910079-6	2000	Based on sulforhodamine B assays for the number of viable cells, the NQO1 clones showed increased sensitivity to EO9, an indoloquinone that undergoes bioactive reduction by NQO1.	Indolequinones	121-134	NAD(P)H quinone dehydrogenase 1	Homo sapiens	173-177
9783730-0	1998	Reduction of the indoloquinone anticancer drug EO9 by purified DT-diaphorase: a detailed kinetic study and analysis of metabolites.	Indolequinones	17-30	NAD(P)H quinone dehydrogenase 1	Rattus norvegicus	63-76
10692564-0	2000	The relative importance of NADPH: cytochrome c (P450) reductase for determining the sensitivity of human tumour cells to the indolequinone EO9 and related analogues lacking functionality at the C-2 and C-3 positions.	Indolequinones	125-138	cytochrome c, somatic	Homo sapiens	34-46
9822546-0	1998	Indolequinone antitumor agents: correlation between quinone structure, rate of metabolism by recombinant human NAD(P)H:quinone oxidoreductase, and in vitro cytotoxicity.	Indolequinones	0-13	crystallin zeta	Homo sapiens	119-141
9822546-1	1998	A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (NQO1) were studied.	Indolequinones	12-26	2,4-dienoyl-CoA reductase 1	Homo sapiens	170-177
9822546-1	1998	A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (NQO1) were studied.	Indolequinones	12-26	crystallin zeta	Homo sapiens	178-200
10514277-0	1999	Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.	Indolequinones	39-53	NAD(P)H quinone dehydrogenase 1	Homo sapiens	63-76
10465544-2	1999	Overall, the quinolinequinones were much better substrates for NQO1 than analogous indolequinones, with compounds containing heterocyclic substituents at C-2 being among the best substrates.	Indolequinones	83-97	complement C2	Homo sapiens	154-157
9783730-1	1998	DT-diaphorase has been implicated in the activation and mechanism of cytotoxicity of the investigational indoloquinone anticancer drug EO9.	Indolequinones	105-118	NAD(P)H quinone dehydrogenase 1	Rattus norvegicus	0-13
7526885-0	1994	DT-diaphorase protects cells from the hypoxic cytotoxicity of indoloquinone EO9.	Indolequinones	62-75	NAD(P)H quinone dehydrogenase 1	Homo sapiens	0-13
7547240-1	1995	DT-diaphorase (DTD) is an important enzyme for the bioreductive activation of the new alkylating indoloquinone EO9.	Indolequinones	97-110	NAD(P)H quinone dehydrogenase 1	Homo sapiens	0-13
9871615-0	1998	Indolequinone antitumor agents: relationship between quinone structure and rate of metabolism by recombinant human NQO1.	Indolequinones	0-13	NAD(P)H quinone dehydrogenase 1	Homo sapiens	115-119
7536024-0	1995	Indoloquinone EO9: DNA interstrand cross-linking upon reduction by DT-diaphorase or xanthine oxidase.	Indolequinones	0-13	NAD(P)H quinone dehydrogenase 1	Rattus norvegicus	67-80
8509220-5	1993	NIH-3T3 transformants expressing H-ras were less sensitive than those expressing trk or the wild type to the indoloquinone EO9, methotrexate and arabino-furanosylcytosine.	Indolequinones	109-122	Harvey rat sarcoma virus oncogene	Mus musculus	33-38
7514407-1	1994	EO9, a new bioreductive indoloquinone alkylating agent, requires activation by a two-electron reduction, which can be catalysed by the NAD(P)H:quinone oxidoreductase DT-diaphorase (DTD) (EC 1.6.99.2).	Indolequinones	24-37	NAD(P)H quinone dehydrogenase 1	Homo sapiens	166-179
8262670-1	1994	Studies with purified DT-diaphorase have shown that the enzyme is capable of catalyzing a two-electron reduction of the novel indoloquinone EO9 to a DNA-damaging alkylating species.	Indolequinones	126-139	NAD(P)H quinone dehydrogenase 1	Homo sapiens	22-35
7813420-6	1994	The data demonstrate that the specific melanogenic function of TRP1 is the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to a carboxylated indole-quinone at a down-stream point in the melanin biosynthetic pathway.	Indolequinones	152-166	tyrosinase-related protein 1	Mus musculus	63-67
12231940-6	1993	The study of tyramine structure-activity relationships further suggested that the toxicity of tyramine might be due to the formation of indolequinones after oxidation by PPO.	Indolequinones	136-150	protoporphyrinogen oxidase, chloroplastic	Nicotiana tabacum	170-173
8509220-5	1993	NIH-3T3 transformants expressing H-ras were less sensitive than those expressing trk or the wild type to the indoloquinone EO9, methotrexate and arabino-furanosylcytosine.	Indolequinones	109-122	neurotrophic tyrosine kinase, receptor, type 1	Mus musculus	81-84
24666648-3	2014	A series of indolequinones (known substrates of NQO1) was synthesized and coupled to bexarotene.	Indolequinones	12-26	NAD(P)H quinone dehydrogenase 1	Homo sapiens	48-52
1389472-0	1992	DT-diaphorase activity correlates with sensitivity to the indoloquinone EO9 in mouse and human colon carcinomas.	Indolequinones	58-71	NAD(P)H dehydrogenase, quinone 1	Mus musculus	0-13
1544832-0	1992	Structure-activity relationships for DT-diaphorase reduction of hypoxic cell directed agents: indoloquinones and diaziridinyl benzoquinones.	Indolequinones	94-108	NAD(P)H quinone dehydrogenase 1	Homo sapiens	37-50
1714284-0	1991	The role of NAD(P)H: quinone reductase (EC 1.6.99.2, DT-diaphorase) in the reductive bioactivation of the novel indoloquinone antitumor agent EO9.	Indolequinones	112-125	NAD(P)H quinone dehydrogenase 1	Homo sapiens	53-66
5671234-3	1968	Indoloquinone analogs with further variations at C-5.	Indolequinones	0-13	complement C5	Homo sapiens	49-52
5907867-3	1966	Indoloquinone analogs with variations at C-5.	Indolequinones	0-13	complement C5	Homo sapiens	41-44
28395199-0	2017	Design, synthesis, and biological evaluation of NAD(P)H: Quinone oxidoreductase (NQO1)-targeted oridonin prodrugs possessing indolequinone moiety for hypoxia-selective activation.	Indolequinones	125-138	crystallin zeta	Homo sapiens	57-79
28395199-0	2017	Design, synthesis, and biological evaluation of NAD(P)H: Quinone oxidoreductase (NQO1)-targeted oridonin prodrugs possessing indolequinone moiety for hypoxia-selective activation.	Indolequinones	125-138	NAD(P)H quinone dehydrogenase 1	Homo sapiens	81-85
33768386-3	2021	Novel indolequinone compounds have been shown, in pancreatic cancer models, to inhibit thioredoxin reductase activity and exhibit potent anticancer activity.	Indolequinones	6-19	thioredoxin	Homo sapiens	87-98
33768386-9	2021	This study provides important evidence of the roles of the thioredoxin system as an exploitable radiobiological target in breast cancer cells and highlights the potential therapeutic value of indolequinones as radiosensitisers.	Indolequinones	192-206	thioredoxin	Homo sapiens	59-70
6031712-3	1967	Synthesis of indoloquinone analogs with certain C-3 variants.	Indolequinones	13-26	complement C3	Homo sapiens	48-51
25281270-0	2014	Synthesis and in vitro evaluation of radioiodinated indolequinones targeting NAD(P)H: quinone oxidoreductase 1 for internal radiation therapy.	Indolequinones	52-66	NAD(P)H quinone dehydrogenase 1	Homo sapiens	77-110
25281270-3	2014	We designed three NQO1-targeted radioiodinated compounds including two ether linkage compounds ([(125)I]1 and [(125)I]2) and a sulfide linkage compound ([(125)I]3) based on the selective binding of indolequinone analogs to the active site of NQO1 by the stacking effect.	Indolequinones	198-211	NAD(P)H quinone dehydrogenase 1	Homo sapiens	18-22