TRETAZICAR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H8N4O5
Molecular Weight	252.1836
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)C1=CC(N2CC2)=C(C=C1[N+]([O-])=O)[N+]([O-])=O

InChI

InChIKey=WOCXQMCIOTUMJV-UHFFFAOYSA-N

InChI=1S/C9H8N4O5/c10-9(14)5-3-7(11-1-2-11)8(13(17)18)4-6(5)12(15)16/h3-4H,1-2H2,(H2,10,14)

HIDE SMILES / InChI

Molecular Formula	C9H8N4O5
Molecular Weight	252.1836
Charge	0
Count

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

Description
Sources: https://adisinsight.springer.com/drugs/800019051 | https://www.ema.europa.eu/en/documents/orphan-designation/eu/3/08/529-public-summary-positive-opinion-orphan-designation-tretazicar-treatment-visceral-leishmaniasis_en.pdf | https://ascopubs.org/doi/abs/10.1200/jco.2008.26.15_suppl.2505

Tretazicar is a dinitrobenzamide prodrug that is converted in the presence of the enzyme NQO2 and co-substrate caricotamide (EP-0152R) into a potent cytotoxic bifunctional alkylating agent. Tretazicar is a product that belongs to a family of products used in the treatment of cancer because of its capacity to kill cells. The enzyme that activates tretazicar is present in leishmania cells where the product can be transformed and be active. Tretazicar kills infected cells by binding to the genetic material (DNA) of the cells and creating bonds that disrupt the genetic material and its function, finally resulting in the death of the infected cell. On 4 February 2008, orphan designation EU/3/08/529 was granted by the European Commission to Morvus Technology Limited, United Kingdom, for tretazicar for the treatment of visceral leishmaniasis. On 4 February 2008, orphan designation EU/3/08/529 was granted by the European Commission to Morvus Technology Limited, United Kingdom, for tretazicar for the treatment of visceral leishmaniasis. Tretazicar had been in phase II clinical trial for the treatment of liver cancer. However, this development was discontinued.

Originator

Approval Year

PubMed

Title	Date	PubMed
Appropriate subcellular localisation of prodrug-activating enzymes has important consequences for suicide gene therapy.	2001 Jul 1	11391631
[The trends in new drugs for the prostate cancer].	2002 Dec	12599585
Inhibition of myc-dependent breast tumor formation in transgenic mice.	2002 Jan	11859878
CB 1954: from the Walker tumor to NQO2 and VDEPT.	2003	14529407
Effect of nitroreduction on the alkylating reactivity and cytotoxicity of the 2,4-dinitrobenzamide-5-aziridine CB 1954 and the corresponding nitrogen mustard SN 23862: distinct mechanisms of bioreductive activation.	2003 Apr	12703963
Professor Tom Connors and the development of novel cancer therapies by the Phase I/II Clinical Trials Committee of Cancer Research UK.	2003 Aug 4	12888809
Clostridia in cancer therapy.	2003 Dec	15035028
Bystander cell killing spreading from endothelial to tumor cells in a three-dimensional multicellular nodule model after Escherichia coli nitroreductase gene delivery.	2003 Nov 28	14623255
Generation of Escherichia coli nitroreductase mutants conferring improved cell sensitization to the prodrug CB1954.	2003 Sep 1	14500391
Mechanism of cell death induced by the novel enzyme-prodrug combination, nitroreductase/CB1954, and identification of synergism with 5-fluorouracil.	2003 Sep 1	12942130
Studies on the nitroreductase prodrug-activating system. Crystal structures of complexes with the inhibitor dicoumarol and dinitrobenzamide prodrugs and of the enzyme active form.	2003 Sep 11	12954054
The nitroreductase/CB1954 enzyme-prodrug system.	2004	14657579
Methods to improve efficacy in suicide gene therapy approaches: targeting prodrug-activating enzymes carboxypeptidase G2 and nitroreductase to different subcellular compartments.	2004	14657569
Enhanced efficacy of Escherichia coli nitroreductase/CB1954 prodrug activation gene therapy using an E1B-55K-deleted oncolytic adenovirus vector.	2004 Jul	15164095
Enzyme-catalyzed activation of anticancer prodrugs.	2004 Mar	15001663
2-Amino metabolites are key mediators of CB 1954 and SN 23862 bystander effects in nitroreductase GDEPT.	2004 Mar 8	14997211
Antitumor immune responses mediated by adenoviral GDEPT using nitroreductase/CB1954 is enhanced by high-level coexpression of heat shock protein 70.	2005 Jun	15665820
Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954.	2005 Oct 14	16129418
Kinetic and structural characterisation of Escherichia coli nitroreductase mutants showing improved efficacy for the prodrug substrate CB1954.	2007 Apr 27	17350040
Metabolic activation of the antitumor drug 5-(Aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) by NO synthases.	2008 Apr	18370414
Escherichia coli nitroreductase plus CB1954 enhances the effect of radiotherapy in vitro and in vivo.	2008 Mar	18079753
E. coli nitroreductase/CB1954 gene-directed enzyme prodrug therapy: role of arylamine N-acetlytransferase 2.	2008 Nov	18600257
A mammalianized synthetic nitroreductase gene for high-level expression.	2009 Aug 27	19712451

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:16:18 GMT 2023` Edited by `admin` on `Fri Dec 15 16:16:18 GMT 2023`
Record UNII	7865D5D01M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRETAZICAR

Official Name

English

5-(AZIRIDIN-1-YL)-2,4-DINITROBENZAMIDE

Systematic Name

English

NSC-115829

Code

English

CB-1954

Code

English

tretazicar [INN]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/08/529