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| 50mg |
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Purity: ≥98%
Tretazicar (CB-1954; CB1954), a dinitrobenzamide analog and prodrug, is a potent and highly selective DNA alkylating agent that generates highly cytotoxic interstrand crosslinks in DNA.It is transformed, in the presence of the co-substrate caricotamide (EP-0152R) (EP) and the enzyme NQO2, into a strong cytotoxic bifunctional DNA-alkylating agent. CB1954 has been suggested for use with the Escherichia coli enzyme nitroreductase (Ntr) in enzyme-prodrug gene therapy systems. After CB1954 is converted by Ntr to 2- and 4-hydroxylamino analogues, the 4-hydroxylamino analogue reacts non-enzymatically with cellular thio-esters to produce a strong cytotoxic bifunctional alkylating agent that can cross-link DNA.
| ln Vitro |
The monofunctional alkylating agent CB1954 can be transformed into a toxic form by overexpressing nitroreductase oxidored nitro domain containing protein 1 (NOR1), which reduces the potent cytotoxin CB1954's 4 nitro group. When used on the NPC cell line CNE1, toxic CB1954 increases cell death. Grb2 expression is upregulated and MAPK signal transduction is activated in the HepG2 cell line by the NOR1 gene, which increases CB1954-mediated cell cytotoxicity [1].
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| ln Vivo |
In vivo, the NTR/CB1954 system is used to specifically ablate cells. This inducible ablation system has a dose-dependent effect[3]. Cell proliferation is not necessary for CB1954-mediated NTR-mediated cell killing. DNA cross-linking caused by the activated CB1954 likely starts the apoptosis cascade and swiftly kills off cells. Functional p53 is not necessary for NTR-CB1954 to kill cells in a targeted and efficient manner[2].
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| Cell Assay |
The human hepatocellular carcinoma cells, HepG2, are kept in a humidified culture incubator at 37˚C with 5% CO2 and 95% air, supplemented with 10% fetal calf serum (FCS). Cell cytotoxicity tests are carried out in accordance with earlier guidelines. After reaching approximately 80% confluence, HepG2 cells are treated with CB1954 or a signal transduction inhibitor after being rinsed with PBS. In each experiment, measurements are taken from ten to twelve different microscopic fields, and data are compiled from three to five experiments.
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| Animal Protocol |
RED 40 female mice expressing high levels of BLG-NTR transgene in the mammary gland and nontransgenic control mice on lactation day 6
50 mg/kg i.p. |
| References |
| Molecular Formula |
C9H8N4O5
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|---|---|
| Molecular Weight |
252.1836
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| Exact Mass |
252.05
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| Elemental Analysis |
C, 42.86; H, 3.20; N, 22.22; O, 31.72
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| CAS # |
21919-05-1
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| Appearance |
White solid powder
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| SMILES |
C1CN1C2=C(C=C(C(=C2)C(=O)N)[N+](=O)[O-])[N+](=O)[O-]
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| InChi Key |
WOCXQMCIOTUMJV-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
5-(aziridin-1-yl)-2,4-dinitrobenzamide
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| Synonyms |
CB-1954; CB1954; CB 1954
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 50~125 mg/mL (198.3~495.7 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9654 mL | 19.8271 mL | 39.6542 mL | |
| 5 mM | 0.7931 mL | 3.9654 mL | 7.9308 mL | |
| 10 mM | 0.3965 mL | 1.9827 mL | 3.9654 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00746590 | Terminated | Drug: Prolarix (tretazicar co-administered with caricotamide) |
Hepatocellular Carcinoma | BTG International Inc. | September 2008 | Phase 2 |
| NCT04374240 | Completed | Genetic: AdNRGM | Prostate Cancer | University of Birmingham | March 19, 2013 | Phase 1 |
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