Page last updated: 2024-12-11

apaziquone

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

apaziquone: structure given in first source; RN given refers to (E)-isomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID5813717
CHEMBL ID73822
CHEBI ID177558
SCHEMBL ID367965
SCHEMBL ID367964
MeSH IDM0507513

Synonyms (55)

Synonym
nsc-382456
CHEMBL73822
CHEBI:177558
5-(aziridin-1-yl)-3-(hydroxymethyl)-2-[(e)-3-hydroxyprop-1-enyl]-1-methylindole-4,7-dione
e-85/050
eo9 ,
nor-701
neoquin
e-85/053
apaziquone
eoquin
eo-9
nsc 382456
1h-indole-4,7-dione, 5-(1-aziridinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1-methyl-, (e)-
apaziquonum
apaziquonum [inn-latin]
1h-indole-4,7-dione, 5-(1-aziridinyl)-3-(hydroxymethyl)-2-((1e)-3-hydroxy-1-propenyl)-1-methyl-
(e)-5-(1-azirinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1-methyl-1h-indole-4,7-dione
e 09
eo 9 (pharmaceutical)
5-(azridin-1-yl)-3-(hydroxymethyl)-2-((1e)-3-hydroxyprop-1-enyl)-methyl-1h-indole-4,7-dione
apaziquone [usan:inn]
nsc 382459
apaziquone (usan/inn)
D02965
114560-48-4
eoquin (tn)
1h-indole-4, 5-(1-aziridinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1-methyl-
nsc382459
E09 ,
nsc-382459
antineoplastic-382459
qapzola
5-(aziridin-1-yl)-3-(hydroxymethyl)-2-(3-hydroxyprop-1-enyl)-1-methylindole-4,7-dione
BCP9000309
h464zo600o ,
unii-h464zo600o
apaziquone [inn]
apaziquone [mi]
apaziquone [usan]
5-(azridin-1-yl)-3-(hydroxymethyl)-2-[(1e)-3-hydroxyprop-1-enyl]-methyl-1h-indole-4,7-dione
SCHEMBL367965
SCHEMBL367964
141304-51-0
5-aziridin-1-yl-3-hydroxymethyl-2-((e)-3-hydroxy-propenyl)-1-methyl-1h-indole-4,7-dione
1h-indole-4,7-dione, 5-(1-aziridinyl)-3-(hydroxymethyl)-2-[(1e)-3-hydroxy-1-propen-1-yl]-1-methyl-
DB12593
CS-0006128
Q4779259
5-(1-aziridinyl)-3-(hydroxymethyl)-2-[(1e)-3-hydroxy-1-propen-1-yl]-1-methyl-1h-indole-4,7-dione;
n1,n6-diethyl-3-methylhexanediamide
(e)-5-(1-aziridinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1-methyl-1h-indole-4,7-dione
5-(1-aziridinyl)-3-(hydroxymethyl)-2-[(1e)-3-hydroxy-1-propen-1-yl]-1-methyl-1h-indole-4,7-dione
DTXSID90869587
AKOS040744809

Research Excerpts

Overview

Apaziquone is a promising local agent for the treatment and prevention of recurrent urothelial carcinoma of the bladder. More research is needed to prove its actual benefit.

ExcerptReferenceRelevance
"Apaziquone is an interesting drug for intravesical use in patients with nonmuscle invasive bladder cancer; however, more research is needed to prove its actual benefit. "( Apaziquone for Nonmuscle Invasive Bladder Cancer: Where Are We Now?
Alfred Witjes, J; Arends, TJH, 2020
)
3.44
"Apaziquone is a promising drug for intravesical use in patients with NMIBC."( Apaziquone for non-muscle invasive bladder cancer: a critical review.
Kolli, PS; Witjes, JA, 2008
)
3.23
"Apaziquone is a promising local agent for the treatment and prevention of recurrent urothelial carcinoma of the bladder. "( Apaziquone as an intravesical therapeutic agent for urothelial non-muscle-invasive bladder cancer.
Chin, J; Yutkin, V, 2012
)
3.26
"EO9 (Apaziquone) is a bioreductive drug that has a chequered history. "( EO9 (Apaziquone): from the clinic to the laboratory and back again.
Hendriks, HR; Peters, GJ; Phillips, RM, 2013
)
1.42
"EO9 (apaziquone) is a novel, promising anticancer agent, which is currently being investigated for the intravesical treatment of bladder cancer. "( Stability experiments in human urine with EO9 (apaziquone): a novel anticancer agent for the intravesical treatment of bladder cancer.
Beijnen, JH; Lenaz, L; Mirejovsky, D; Rosing, H; Schellens, JH; Vainchtein, LD, 2007
)
1.11

Treatment

ExcerptReferenceRelevance
"Apaziquone treatment inhibited cell proliferation and induced apoptosis in OSCC cells in vitro."( Anticancer Activity of Apaziquone in Oral Cancer Cells and Xenograft Model: Implications for Oral Cancer Therapy.
Ralhan, R; Somasundaram, RT; Srivastava, G; Walfish, PG, 2015
)
1.45

Toxicity

ExcerptReferenceRelevance
" This suggests either that the one-electron reduction product of EO9 metabolism, the semiquinone, is more toxic than the two-electron reduction product, the hydroquinone, or that the hydroquinone is not cytotoxic and aerobic toxicity is due to the transient appearance of the semiquinone upon back oxidation of the hydroquinone."( DT-diaphorase protects cells from the hypoxic cytotoxicity of indoloquinone EO9.
Gerritsen, M; Plumb, JA; Workman, P, 1994
)
0.29
"7 mg/m2), the recommended starting dose for clinical phase I studies, was found to be safe in rats."( EO9: a novel bioreductive alkylating indoloquinone with preferential solid tumour activity and lack of bone marrow toxicity in preclinical models.
Berger, DP; Bibby, MC; Boven, E; Double, JA; Dreef-van der Meulen, HC; Fiebig, HH; Hendriks, HR; Henrar, RE; Kooistra, KL; Pizao, PE, 1993
)
0.29
" Adverse events and safety parameters were assessed on days 8 and 15 after transurethral bladder tumor resection."( Safety and side effects of immediate instillation of apaziquone following transurethral resection in patients with nonmuscle invasive bladder cancer.
Gershman, A; Gleason, D; Hendricksen, K; Lerner, S; Saltzstein, D; Witjes, JA; Young, JM, 2008
)
0.6

Pharmacokinetics

ExcerptReferenceRelevance
" In all cases, considerable effort has gone into detailed pharmacokinetic studies conducted before and during the clinical phase I studies."( Pharmacokinetics and early clinical studies of selected new drugs.
Cassidy, J; Graham, MA; Jodrell, D; Kaye, SB; Workman, P, 1993
)
0.29
" Pharmacokinetic studies were performed with the first and third dose of therapy and nine blood samples were obtained over 30 min postinfusion."( Phase I pharmacokinetics and limited sampling strategies for the bioreductive alkylating drug EO9. EORTC Early Clinical Trials Group.
Aamdal, S; Graham, MA; Groot, Y; Lund, B; McLeod, HL; Setanoians, A, 1996
)
0.29
"Population pharmacokinetic-dynamic analysis was prospectively integrated in the clinical phase II programme of EO9 to determine the population pharmacokinetic profile in a larger population of patients, to estimate individual patient pharmacokinetic parameters, and to investigate relationships between drug exposure and clinical outcome."( Population pharmacokinetics and dynamics in phase II studies of the novel bioreductive alkylating cytotoxic indoloquinone EO9.
Calabresi, F; Cassidy, J; Cox, EH; Dirix, L; Dombernowsky, P; Epelbaum, R; Hanauske, AR; Loos, WJ; Monfardini, S; Paridaens, R; Pavlidis, N; Schellens, JH; Verweij, J; Wanders, J; Wolff, J, 2001
)
0.31

Dosage Studied

ExcerptRelevanceReference
"The aim of this study was to design a stable parenteral dosing form of the investigational cytotoxic drug, encoded EO9."( Pharmaceutical development of a parenteral lyophilized formulation of the novel indoloquinone antitumor agent EO9.
Beijnen, JH; Bult, A; Henrar, RE; Jonkman-de Vries, JD; Kettenes-van den Bosch, JJ; Talsma, H, 1994
)
0.29
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
indolesAny compound containing an indole skeleton.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (18)

Assay IDTitleYearJournalArticle
AID217040In vitro concentration required to kill 50% of the aerobic cells1997Journal of medicinal chemistry, Jul-18, Volume: 40, Issue:15
2-Cyclopropylindoloquinones and their analogues as bioreductively activated antitumor agents: structure-activity in vitro and efficacy in vivo.
AID233456Selectivity ratio of IC50 of BE and HT-29 cells1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID212880Hypoxic cytotoxic ratios of the concentration required to kill 50% of the aerobic cells and concentration required to kill hypoxic cells1997Journal of medicinal chemistry, Jul-18, Volume: 40, Issue:15
2-Cyclopropylindoloquinones and their analogues as bioreductively activated antitumor agents: structure-activity in vitro and efficacy in vivo.
AID300737Cytotoxicity against high NQO1 protein expressing human H460 cells by MTT assay2007Bioorganic & medicinal chemistry, Oct-01, Volume: 15, Issue:19
Synthesis of cryptolepine analogues as potential bioreducible anticancer agents.
AID217041In vitro concentration required to kill hypoxic cells V79-379A cells1997Journal of medicinal chemistry, Jul-18, Volume: 40, Issue:15
2-Cyclopropylindoloquinones and their analogues as bioreductively activated antitumor agents: structure-activity in vitro and efficacy in vivo.
AID144376Substrate specificity towards human NAD(P)H quinone reductase1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID300739Activity of recombinant human NQO1 assessed as specific activity2007Bioorganic & medicinal chemistry, Oct-01, Volume: 15, Issue:19
Synthesis of cryptolepine analogues as potential bioreducible anticancer agents.
AID144375Inhibitory activity against human NAD(P)H quinone reductase at 50 uM1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID80648Chemosensitivity against DT-diaphorase rich H29 cell lines1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID8478Chemosensitivity against DT-diaphorase rich A549 cell lines1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID233455Selectivity ratio of IC50 of BE and A549 cells1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID41359Chemosensitivity against DT-diaphorase deficient BEcell lines1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID226464Hypoxic cytotoxicity ratio determined in V79-379A cells1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID300738Cytotoxicity against low NQO1 protein expressing human BE cells by MTT assay2007Bioorganic & medicinal chemistry, Oct-01, Volume: 15, Issue:19
Synthesis of cryptolepine analogues as potential bioreducible anticancer agents.
AID300741Selectivity ratio of IC50 for human H460 cells IC50 for human BE cells2007Bioorganic & medicinal chemistry, Oct-01, Volume: 15, Issue:19
Synthesis of cryptolepine analogues as potential bioreducible anticancer agents.
AID144374Ability to serve as substrate for human NAD(P)H quinone reductase determined by measuring reduction of cytochrome C at 550 nM1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID233084Ratio of IC50 of BE to IC50 of A5491999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (100)

TimeframeStudies, This Drug (%)All Drugs %
pre-19901 (1.00)18.7374
1990's58 (58.00)18.2507
2000's27 (27.00)29.6817
2010's10 (10.00)24.3611
2020's4 (4.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 25.49

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index25.49 (24.57)
Research Supply Index4.75 (2.92)
Research Growth Index6.91 (4.65)
Search Engine Demand Index26.67 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (25.49)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials12 (11.65%)5.53%
Reviews23 (22.33%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other68 (66.02%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (9)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Randomized, Multicenter, Two-Arm, Single-Dose, Double-Blind, Placebo-CONtrolled Phase 3 Study of Intravesical Qapzola™ (Apaziquone) as a Chemotherapy Adjuvant to TransUrEthral Resection of Bladder Tumors in Patients With Low- to Intermediate-Risk Non-Mu [NCT03224182]Phase 3118 participants (Actual)Interventional2017-08-04Terminated(stopped due to Suspended development)
Phase I Clinical Trial to Evaluate the Safety and Pharmacokinetics of Intravesical Instillation of EO9 in Patients With Non-muscle Invasive Bladder Cancer(NMIBC) [NCT01373398]Phase 111 participants (Actual)Interventional2011-05-31Completed
A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 3 Trial of Single-Dose Intravesical Apaziquone (EOquin®) as a Surgical Adjuvant Instilled in the Early Postoperative Period in Patients Undergoing Transurethral Resection for Noninvasive B [NCT00598806]Phase 3812 participants (Actual)Interventional2007-08-31Completed
Phase II Study of Intravesical Instillation of EOQUIN™ in High Risk Superficial Bladder Cancer [NCT00141531]Phase 253 participants (Actual)Interventional2005-07-31Completed
Randomized, Placebo-controlled, Double-blinded Study of Single Immediate Instillation of EO9 After TURBT in Patients With NMIBC [NCT01475266]Phase 2/Phase 351 participants (Actual)Interventional2011-11-30Terminated(stopped due to Sponsor's decision)
A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 3 Trial of Single Dose Intravesical Apaziquone (EOquin®) as a Surgical Adjuvant Instilled in the Early Postoperative Period in Patients Undergoing Transurethral Resection for Noninvasive B [NCT00461591]Phase 3802 participants (Actual)Interventional2007-04-30Completed
A Phase 3 International, Multicenter, Double-Blind, Placebo-Controlled, Randomized Trial Evaluating the Efficacy and Safety of Multiple Instillations of Intravesical Apaziquone vs. Placebo in Patients With Low-Intermediate Risk Non-Muscle Invasive Bladder [NCT01410565]Phase 366 participants (Actual)Interventional2011-07-31Terminated(stopped due to Business reason)
A Phase 3 International, Double-Bind Trial Evaluating Efficacy and Safety of Multiple Instillations of Intravesical Apaziquone vs. Placebo in Patients With Low-Intermediate Risk Non-Muscle Invasive Bladder Cancer (NMIBC) [NCT01469221]Phase 347 participants (Actual)Interventional2012-01-31Terminated(stopped due to Business reason)
A Multicenter, Multi-Arm, Randomized, Multi-Dose, Placebo-Controlled, Double-Blind, Phase 3 Study of Intravesical Apaziquone (EOquin®) as a Surgical Adjuvant in the Immediate Postoperative Period in Patients Undergoing Transurethral Resection for Non- Mus [NCT02563561]Phase 362 participants (Actual)Interventional2015-10-09Terminated
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00461591 (6) [back to overview]Disease Free Interval
NCT00461591 (6) [back to overview]Disease Free Survival
NCT00461591 (6) [back to overview]Number of Recurrences Per Patient
NCT00461591 (6) [back to overview]Overall Survival
NCT00461591 (6) [back to overview]Time to Progression
NCT00461591 (6) [back to overview]Time to Recurrence
NCT00598806 (6) [back to overview]Disease-Free Interval
NCT00598806 (6) [back to overview]Disease-Free Survival
NCT00598806 (6) [back to overview]Number of Recurrences Per Patient
NCT00598806 (6) [back to overview]Overall Survival
NCT00598806 (6) [back to overview]Time to Progression
NCT00598806 (6) [back to overview]Time to Recurrence
NCT01410565 (3) [back to overview]Participants With Treatment Emergent Adverse Events (TEAEs)
NCT01410565 (3) [back to overview]Recurrence Rate at 24 Months
NCT01410565 (3) [back to overview]Time to Recurrence
NCT01469221 (2) [back to overview]2-Year Recurrence Rate
NCT01469221 (2) [back to overview]Time to Recurrence
NCT02563561 (1) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and Death
NCT03224182 (1) [back to overview]Number of Participants With Treatment-emergent Adverse Event (TEAE), Treatment-related Adverse Events, Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation, TEAEs of Special Interest, and Death

Disease Free Interval

The number of months from randomization to histologically confirmed progression of the patient's bladder tumor or death from any cause (NCT00461591)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone22.9
Placebo22.0

[back to top]

Disease Free Survival

The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor or death from any cause (NCT00461591)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone18.0
Placebo16.4

[back to top]

Number of Recurrences Per Patient

The number of histologically confirmed recurrences during the course of the study. (NCT00461591)
Timeframe: 2 years

Interventiontimes (Mean)
Apaziquone0.6
Placebo0.9

[back to top]

Overall Survival

The number of months from randomization to death from any cause. (NCT00461591)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone20.3
Placebo23.7

[back to top]

Time to Progression

The number of months from randomization to progression to either a higher stage or grade of the patient's bladder tumor. (NCT00461591)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone22.9
Placebo22.0

[back to top]

Time to Recurrence

The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor. (NCT00461591)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone18.3
Placebo16.7

[back to top]

Disease-Free Interval

The number of months from randomization to histologically confirmed progression of the patient's bladder tumor or death from any cause (NCT00598806)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone22.7
Placebo21.9

[back to top]

Disease-Free Survival

The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor or death from any cause (NCT00598806)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone17.9
Placebo16.4

[back to top]

Number of Recurrences Per Patient

The number of histologically confirmed recurrences during the course of the study. (NCT00598806)
Timeframe: 2 years

Interventionrecurrences (Mean)
Apaziquone0.6
Placebo0.9

[back to top]

Overall Survival

The number of months from randomization to death from any cause. (NCT00598806)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone24
Placebo20.2

[back to top]

Time to Progression

The number of months from randomization to progression to either a higher stage or grade of the patient's bladder tumor. (NCT00598806)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone22.7
Placebo21.9

[back to top]

Time to Recurrence

The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor. (NCT00598806)
Timeframe: 2 years

Interventionmonths (Mean)
Apaziquone18.1
Placebo16.7

[back to top]

Participants With Treatment Emergent Adverse Events (TEAEs)

TEAEs will be mainly characterized by the number of treatment emergent adverse events and treatment related AEs that occur or worsen after the first dose of study treatment. (NCT01410565)
Timeframe: 24 Months from Randomization

Interventionparticipants (Number)
Apaziquone11
Placebo12

[back to top]

Recurrence Rate at 24 Months

Measurement the number of participants with the recurrence at 24 months. (NCT01410565)
Timeframe: 24 months

Interventionparticipants (Number)
Apaziquone1
Placebo4

[back to top]

Time to Recurrence

Time to recurrence is the time from randomization to the date of first histologically confirmed recurrence of bladder cancer (for eligible patients with Low- intermediate risk NMIBC, who had undergone TURBT followed by, a single instillation of apaziquone immediately post TURBT and multiple instillations of apaziquone or placebo). (NCT01410565)
Timeframe: Recurrence of cancer in the bladder during 24 months of follow-up

Interventionmonths (Mean)
Apaziquone9.2
Placebo7.3

[back to top]

2-Year Recurrence Rate

Proportion of patients with recurrence at or before 24 months (NCT01469221)
Timeframe: 24 Months

InterventionParticipants (Count of Participants)
Apaziquone1
Placebo6

[back to top]

Time to Recurrence

Time from randomization to the date of first histologically confirmed recurrence of bladder cancer (NCT01469221)
Timeframe: 24 Months

Interventionmonths (Median)
ApaziquoneNA
Placebo8.5

[back to top] [back to top] [back to top]