 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C12H15N3O6 |
| Molecular Weight | 297.26 |
| Exact Mass | 297.096 |
| CAS # | 2451-62-9 |
| Related CAS # | 28825-96-9 |
| PubChem CID | 17142 |
| Appearance | White to off-white solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 501.1±15.0 °C at 760 mmHg |
| Melting Point | 95-98°C |
| Flash Point | 256.9±20.4 °C |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C |
| Index of Refraction | 1.635 |
| LogP | -2.77 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 21 |
| Complexity | 416 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | OUPZKGBUJRBPGC-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C12H15N3O6/c16-10-13(1-7-4-19-7)11(17)15(3-9-6-21-9)12(18)14(10)2-8-5-20-8/h7-9H,1-6H2 |
| Chemical Name | 1,3,5-tris(oxiran-2-ylmethyl)-1,3,5-triazinane-2,4,6-trione |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | Triglycidyl isocyanurate (0–30 μM; 48 hours) suppresses the growth of human non-small-cell lung cancer spheroids in culture and causes the tumorspheres of A549, H460, and H1299 cells to gradually shrink[1]. Triglycidyl isocyanurate (0-30 μM; 48 hours) decreases the expression of Akt1/2/3 and phosphorylated Aktser473/474/472 of A549, H460, and H1299 tumorspheres; however, only A549 and H460 tumorspheres exhibit evident PARP and procaspase-3 cleavage along with the emergent active caspase-3 fragment[1]. Isocyanurate triglycidyl |
| ln Vivo | In subcutaneous injection, tiglycidyl isocyanurate (1.8 and 3.6 mg/kg; every 2-3 days for a total of seven times; 30 days) inhibits the formation of xenograft tumors and has no effect on the weight of the mice in the nude[2]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: A549, H460 and H1299 cells Tested Concentrations: 0 μM; 5 μM; 10 μM; 30 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited tumor cells growth in soft agar. Western Blot Analysis[1] Cell Types: A549, H460 and H1299 cells Tested Concentrations: 0 μM; 5 μM; 10 μM; 30 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited akt1/2/3 expression and p-aktser473/474/472 expression of A549, H460 and H1299 tumorspheres |
| Animal Protocol |
Animal/Disease Models: Female nu/nu (nude) mice with Huh7 cells subcutaneously (sc) injected into the dorsal area[2] Doses: 1.8 mg/kg and 3.6 mg/kg Route of Administration: subcutaneous (sc)injection; every 2 –3 days for total seven times; 30 days Experimental Results: Inhibited the growth of xenograft tumors. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion In an oral (gavage) study in mice, at least 17% of the administered dose was absorbed within 24 hr, with blood analysis indicating that the absorption of triglycidyl isocyanurate administered in aqueous solution was twice that of triglycidyl isocyanurate in sesame oil. Triglycidyl isocyanurate was distributed to the liver, stomach, and testes (the only tissues studied). The only available human data are from clinical trials with alpha-triglycidyl isocyanurate (intravenous administration), which indicate that alpha-triglycidyl isocyanurate has ... total body clearance of 5.7 L/min. Less than 1% of the administered dose was recovered unchanged in urine within 24 hr. In oral (gavage) and intravenous studies with [14C]alpha-triglycidyl isocyanurate in rabbits, the radioactivity recovered in urine within 24 hr was approximately 30% and 60-70%, respectively. Metabolism / Metabolites In an oral (gavage) study in mice, ... blood plasma analysis indicated that triglycidyl isocyanurate was metabolized by hydrolysis to the diol diepoxide, the bis-diol epoxide, and the fully hydrolysed tris-diol, with no free triglycidyl isocyanurate detected 8 hr after treatment. In in vitro studies, rapid hydrolysis of triglycidyl isocyanurate involving the enzyme epoxide hydrolase was observed in mouse liver preparations. Hydrolysis was also observed in rat liver preparations but not in rat lung preparations. Microsomal epoxide hydrolase activity with triglycidyl isocyanurate as substrate measured in two human livers obtained from kidney donors was found to be greater than the activity in rat liver. ... Metabolism of TGIC involves hydrolysis of the epoxy functions, leading to the formation of the trisdiol derivative, and is promoted by hepatic but not pulmonary epoxide hydrolase. Non-enzymatic hydrolysis of the epoxy functions occurs under conditions of low pH. Further mechanisms for the metabolism of TGIC have not been investigated. Excretion of TGIC and/or its metabolites is largely via the urine. Urinary metabolites of TGIC have not been identified. Biological Half-Life In ... intravenous studies with [(14)C]alpha-triglycidyl isocyanurate in rabbits, ... the half-life of triglycidyl isocyanurate in the blood was <5 min. The only available human data are from clinical trials with alpha-triglycidyl isocyanurate (intravenous administration), which indicate that alpha-triglycidyl isocyanurate has a mean half-life in the blood of approximately 1 min ... . |
| Toxicity/Toxicokinetics |
Toxicity Summary IDENTIFICATION AND USE: Triglycidyl isocyanurate (TGT) is a white solid. TGT is used as a crosslinking agent in polymer synthesis, additive in plastic, rubber, and adhesives, hardener in polyester powder coatings, in protective coatings of electronic devices, in top-coated and solder-resistant inks. HUMAN STUDIES: The reported health effects in humans are contact dermatitis and respiratory sensitization. It may also cause serious eye damage. TGT did not induce chromosomal aberrations in human lymphocytes at concentrations up to 2500 ng/mL. Only one aberration was reported at each of the two higher concentrations of 5000 and 10,000 ng/mL. Human trials were performed during clinical development of alpha-TGT as an antitumor agent. In these studies, alpha-TGT was administered iv to cancer patients at doses up to 900 mg/kg bw using a variety of dosing regimes. Toxic signs included myelosuppression, nausea and vomiting, and, rarely, alopecia and leucopenia at high doses (>600 mg/kg bw). Owing to its severe local toxicity (thrombophlebitis) at the site of injection, the use of alpha-TGT as an antitumor agent was not pursued. ANIMAL STUDIES: Acute animal toxicity studies reveal that TGT is toxic by oral and inhalation routes of exposure but has low acute dermal toxicity. TGT produces serious eye irritation. It is a skin sensitizer but not a skin irritant. Short-term repeated dose studies revealed renal, lung, gastric/duodenal, and sperm cell damage. In a subchronic toxicity/fertility study conducted in rats, a dose-dependent reduction in the number of spermatozoa was the only effect observed at concentrations of up to 100 ppm TGT in the diet. The chemical has produced positive results in a range of in vitro genotoxicity studies (gene mutation in bacterial and mammalian cells, unscheduled DNA synthesis, sister chromatid exchanges, and chromosomal aberration assays). Genotoxic effects have also been observed in vivo in somatic (bone marrow) cells and germ cells in the testes. Genotoxicity studies have revealed that the inhalation of TGT produces cytotoxicity and chromosomal aberrations in mouse spermatogonia. A 13-week dietary study in rats has indicated no effects on male fertility. Toxicity Data LC50 (rat) > 650 mg/m3/4h Non-Human Toxicity Values LD50 Rat oral 188-715 mg/kg bw LD50 Rat dermal >2000 mg/kg bw |
| References |
[1]. Teroxirone motivates apoptotic death in tumorspheres of human lung cancer cells. Chem Biol Interact. 2018 Aug 1;291:137-143. [2]. Teroxirone suppresses growth and motility of human hepatocellular carcinoma cells.Biomed Pharmacother. 2018 Mar;99:997-1008. |
| Additional Infomation |
Tris(2,3-epoxypropyl)isocyanurate is a white crystalline solid. (NTP, 1992) Teroxirone is a triazene triepoxide with antineoplastic activity. Teroxine alkylates and cross-links DNA, thereby inhibiting DNA replication. (NCI04) |
Solubility Data
| Solubility (In Vitro) | DMSO : 50 mg/mL (168.20 mM) |
| Solubility (In Vivo) |
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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3641 mL | 16.8203 mL | 33.6406 mL | |
| 5 mM | 0.6728 mL | 3.3641 mL | 6.7281 mL | |
| 10 mM | 0.3364 mL | 1.6820 mL | 3.3641 mL |