apaziquone (E 09)

structure given in first source; RN given refers to (E)-isomer

Also Known As:

E 09; E-09; EO9; 3-hydroxymethyl-5-aziridinyl-1-methyl-2-(1H-indole-4,7-dione)prop-beta-en-alpha-ol; 5-(azridin-1-yl)-3-(hydroxymethyl)-2-((1E)-3-hydroxyprop-1-enyl)-methyl-1H-indole-4,7-dione; EO 9; EO-9; NSC 382,459; NSC 382459; NSC-382459; Qapzola; 1H-Indole-4,7-dione, 5-(1-aziridinyl)-3-(hydroxymethyl)-2- ((1E)-3-hydroxy-1-propenyl)-1-methyl-

Networked: 58 relevant articles (3 outcomes, 21 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Witjes, J Alfred: 6 articles (07/2018 - 04/2005)
2.	Phillips, Roger M: 4 articles (01/2019 - 10/2006)
3.	Puri, Rajiv: 4 articles (06/2009 - 10/2006)
4.	Reddy, Guru: 3 articles (01/2019 - 01/2012)
5.	de Reijke, Theo M: 3 articles (11/2017 - 10/2006)
6.	Phillips, R M: 3 articles (07/2017 - 10/2001)
7.	Hendricksen, Kees: 3 articles (01/2012 - 09/2007)
8.	van der Heijden, Antoine G: 3 articles (06/2009 - 04/2005)
9.	Beijnen, Jos H: 3 articles (08/2007 - 10/2006)
10.	Loadman, Paul M: 2 articles (01/2019 - 10/2006)

Related Diseases

1.	Urinary Bladder Neoplasms (Bladder Cancer) 04/01/2012 - "We studied the safety and efficacy of multiple adjuvant apaziquone instillations in patients with high risk nonmuscle invasive bladder cancer. " 11/01/2017 - "The efficacy of Apaziquone in the treatment of bladder cancer." 01/01/2012 - "The objective of this study was to assess antitumor activity and safety of 3 different formulations of intravesical apaziquone in an orthotopic rat bladder cancer model. " 01/04/2007 - "The outcomes of these stability experiments will be implemented to insure proper sample handling at the clinical sites, transport, storage, and sample handling during analysis in the forthcoming preclinical studies of EO9 in superficial bladder cancer, supported by bioanalysis and pharmacokinetic monitoring." 10/19/2001 - "In a panel of human tumour cell lines, EO9 is selectively toxic towards NQO1 rich cell lines under aerobic conditions and potency can be enhanced by reducing extracellular pH. These studies suggest that a subset of bladder cancer patients exist whose tumours possess the appropriate biochemical machinery required to activate EO9. "
2.	Carcinoma (Carcinomatosis) 01/01/2012 - "The orthotopic Fischer/AY-27 rat bladder urothelial cell carcinoma model to test the efficacy of different apaziquone formulations." 02/01/2012 - "Apaziquone is a promising local agent for the treatment and prevention of recurrent urothelial carcinoma of the bladder. " 06/01/2009 - "Transurethral resection of bladder tumour(s) (TURBT) was performed in patients with multiple pTa-T1 G1-2 urothelial cell carcinoma (UCC) of the bladder, with the exception of one marker lesion of 0.5-1.0 cm. Intravesical apaziquone was administered at weekly intervals for six consecutive weeks, without maintenance instillations. " 10/01/1993 - "This study describes morphological characteristics of multicellular spheroids derived from the human carcinoma cell line, DLD-1 and the evaluation of an investigational bioreductive alkylating agent (EO9) in monolayers, spheroids and xenografts. " 01/01/1992 - "DT-diaphorase activity correlates with sensitivity to the indoloquinone EO9 in mouse and human colon carcinomas."
3.	Non-Muscle Invasive Bladder Neoplasms 01/01/2019 - "These findings impact upon the design of further phase III clinical trials and strongly suggest that apaziquone should not be administered immediately after transurethral resection of non-muscle invasive bladder cancer when haematuria is common." 01/01/2019 - "Inactivation of apaziquone by haematuria: implications for the design of phase III clinical trials against non-muscle invasive bladder cancer." 07/30/2018 - "Two nearly identical Phase 3, multinational, randomized, double-blind, placebo-controlled trials were conducted in patients with histologically confirmed Ta, G1-G2 NMIBC (Target Population) to evaluate the efficacy/safety of a single instillation of apaziquone post-TURBT. " 01/01/2012 - "Apaziquone used intravesically showed significant activity in phase I and II marker lesion studies in non-muscle-invasive bladder cancer. " 06/01/2009 - "To study the time-to-recurrence and duration of response in non-muscle invasive bladder cancer (NMIBC) patients, with a complete ablative response after intravesical apaziquone instillations. "
4.	Neoplasms (Cancer) 01/01/2000 - "The aim of the present phase I study was to determine the toxicities and the maximal tolerated dose (MTD) of EO9 administered as a 5-min i.v. infusion weekly to patients with solid cancers. " 01/01/2015 - "Importantly, apaziquone treatment significantly reduced oral tumor xenograft volume in immunocompromised NOD/SCID/Crl mice without causing apparent toxicity to normal tissues. " 05/01/2009 - "Before apaziquone instillation, the mean +/- SE recurrence rate and tumor rate per year was 1.5 +/- 0.2 and 4.8 +/- 1.2, respectively, and these decreased to 0.6 +/- 0.25 and 1.5 +/- 0.8, respectively, after apaziquone treatment (P <0.05). " 01/01/2000 - "EO9 is a new synthetic bioreductive alkylating indoloquinone, with preferential activity against solid tumors and higher antitumor activity under anaerobic conditions compared with aerobic conditions. " 07/18/1997 - "Both compounds showed antitumor activity both as single agents and in combination with radiation, with some substantial improvements over EO9 (3) at maximum tolerated doses and as single agents against the RIF-1 tumor model and comparable efficacy in the KHT tumor model."
5.	Hypoxia (Hypoxemia) 10/01/2021 - "Potential models were used for interaction studies with hypoxia-specific molecules (tirapazamine, apaziquone, and ENMD) using docking analysis. " 05/15/1994 - "Relative importance of DT-diaphorase and hypoxia in the bioactivation of EO9 by human lung tumor cell lines." 01/01/1994 - "Hypoxia increased the cytotoxicity of cells containing low but not high levels of DT-diaphorase, implying that both 1- and 2-electron reductive activation processes can be important for expression of EO9 toxicity. " 01/01/1994 - "Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro: DT-diaphorase activity and hypoxia." 01/01/1997 - "These data are consistent with cytotoxicity studies that indicate that DT-diaphorase appears to be important in EO9 activation under aerobic conditions, but other enzymes may be more relevant under hypoxia. "

Related Drugs and Biologics

1.	NAD(P)H Dehydrogenase (Quinone) (Quinone Reductase)
2.	Enzymes
3.	Prodrugs
4.	Alkylating Agents
5.	Gemcitabine
6.	Tirapazamine (SR 4233)
7.	hydroxide ion
8.	apaziquone (E 09)
9.	Mitomycin (Mitomycin-C)
10.	quinone (benzoquinone)

Related Therapies and Procedures

1.	Intravesical Administration
2.	Drug Therapy (Chemotherapy)
3.	Transurethral Resection of Bladder
4.	Therapeutics
5.	Aftercare (After-Treatment)