In vitro, mouse lymphoma cells are easily penetrated by trenimon (0.17 mM) [1]. Over time, DNA priming activity is decreased by trenimon (0.17 nM; 5 minutes to 16 hours) [2]. Trenimon (1 nM-10 μM; 10–20 min) suppresses mitosis in a dose-dependent manner and, at a dose of 10 μM, kills HeLa cells after two weeks [3].

Trenimon (0.25 mg/kg; once intraperitoneally) rapidly inhibits peripheral blood cellular components (granulocytes, lymphocytes, reticulocytes, platelets, and red blood cells) and lowers bone marrow cell counts [4]. Trenimon (0.03 mg/kg; intravenously administered once weekly for 52 weeks) has been found to be carcinogenic in vivo [4].

Animal/Disease Models: BR 46 male rats [4]
Doses: 0.03 mg/kg
Route of Administration: intravenous (iv) (iv)injection; 0.03 mg/kg once a week for 52 weeks
Experimental Results: demonstrated carcinogenic effects, 24% of animals developed malignant tumors, And the tumor induction time is 16 months.

Non-Human Toxicity Values
LD50 (Rat, IV): 500 ug/kg LD50 (Rat, IP): 500 ug/kg

[1]. Linford JH. 2,3,5-Tris-ethylenimino-1,4-benzoquinone (Trenimon): some chemical and biological properties. Chem Biol Interact. 1973 Mar;6(3):149-68.
[2]. GRUNICKE H, et al. THE EFFECTS OF THE ALKYLATING CYTOSTATIC AGENT, 2,3,5-TRISETHYLENEIMINO-BENZOQUINONE-1,4(TRENIMON), ON THE PRIMING ABILITY OF DNA FROM MOUSE-ASCITES-TUMOR CELLS IN THE RNA-POLYMERASE-SYSTEM. Biochem Biophys Res Commun. 1965 Feb 3;18:319
[3]. Wegehaupt S, Sehrbundt HJ. Cytologische Untersuchungen an HeLa-Zellen nach kurzfristigen 2,3,5-Trisathyleniminobenzochinon-1,4-Gaben (Trenimon-R) [Cytologic studies on HeLa cells following short-spaced doses of 2,3,5-trisethyleniminobenzoquinone-1,4 (Tren
[4]. Obe G, Beek B. Trenimon: biochemical, physiological and genetic effects on cells and organisms. Mutat Res. 1979 Mar;65(1):21-70.

Triaziquone appears as purple needle-like crystals. (NTP, 1992)
Triaziquone belongs to the 1,4-benzoquinone class of compounds, with its structure consisting of three hydrogen atoms on the 1,4-benzoquinone ring replaced by an aziridin-1-yl group. It possesses alkylating agent and antitumor activity. It belongs to both the aziridinyl and 1,4-benzoquinone classes.
Triaziquone is an alkylating agent based on aziridinylbenzoquinone with potential antitumor activity. The alkylating group in Triaziquone is activated upon quinone reduction to hydroquinone. This ultimately leads to DNA alkylation and cross-linking, thereby inhibiting DNA replication and inducing apoptosis. Furthermore, reactive oxygen species may be generated during the redox cycle, which may contribute to the drug's cytotoxic activity.
Alkylating antitumor drugs are primarily used to treat ovarian tumors. It is toxic to the skin, gastrointestinal tract, bone marrow, and kidneys.

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Mechanism of Action
...Under aerobic conditions, tranimon (250 μM)-induced hepatotoxicity initially induces cyanide-resistant respiration and partially oxidizes glutathione to oxidized glutathione. Hepatocytes rapidly reduce tranimon to hydroquinone. Dicoumarin inhibits hepatocyte DT-dihydroflavinase, increasing tranimon-induced cytotoxicity by approximately 10-fold and significantly inhibiting hydroquinone formation. Both cyanide-resistant respiration and oxidized glutathione formation are significantly increased, leading to oxygen consumption in the culture medium. Subsequently, tranimon is reduced to hydroquinone. ...Under hypoxic conditions, tranimon (350 μM)-induced hepatotoxicity is due to glutathione depletion, without the formation of oxidized glutathione. Under hypoxic conditions, dicoumarin inactivates hepatocyte DT-dihydroflavinase, leading to an approximately 3.5-fold increase in tranimon-induced cytotoxicity and a 2-fold increase in semiquinone radical levels, but its reduction rate remains unaffected. Compared to parental cells (L5178Y), L5178Y/HBM10 lymphoblasts resistant to hydrolyzed benzoquinone mustard were approximately twice as sensitive to taranimon (2,3,5-triethyleneimino-1,4-benzoquinone). It has been reported that L5178Y/HBM10 cells exhibit 24-fold higher DT-dihydroflavinase activity than their parental counterparts. The inhibition of DT-dihydroflavinase by dicumarol significantly suppressed the cytotoxic activity of taranimon against resistant L5178Y/HBM10 cells. Spectrophotometric analysis showed that the reduction rate of quinone compounds taranimon to hydroquinone in L5178Y/HBM10 cells was approximately 25-fold faster than in parental cells, and this reduction reaction could be inhibited by dicumarol. Taranimon also induced sustained cyanide-tolerant respiration in L5178Y cells, but this effect was not observed in resistant L5178Y/HBM10 cells. Treatment of Ehrlich ascites tumor cells with the alkylating agents triazinone [2,3,5-tris(ethyleneimino)benzoquinone-1,4] and nitrogen mustard resulted in decreased post-translational acetylation levels of histones. Acetylation of all core histones was affected. The reduction in acetylation site markers was accompanied by a dose-dependent decrease in the degree of acetylation, which was reflected in H4 acetylation levels. All concentrations of the alkylating agents inhibited histone acetylation, thereby significantly suppressing tumor cell proliferation.

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Therapeutic Use
Antitumor

C12H13N3O2

231.25052

231.101

68-76-8

6235

Purple needles crystals from ethyl acetate

1.727g/cm3

376.5ºC at 760 mmHg

162.5-163ºC

175.1ºC

1.846

-0.1

0

5

3

17

494

0

C1CN1C2=CC(=O)C(=C(C2=O)N3CC3)N4CC4

PXSOHRWMIRDKMP-UHFFFAOYSA-N

InChI=1S/C12H13N3O2/c16-9-7-8(13-1-2-13)12(17)11(15-5-6-15)10(9)14-3-4-14/h7H,1-6H2

2,3,5-tris(aziridin-1-yl)cyclohexa-2,5-diene-1,4-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)