| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
Ribonucleotide reductase (RNR), specifically the M2 subunit. Trimidox acts as a ribonucleotide reductase inhibitor, binding to the iron center of the M2 subunit and blocking the conversion of ribonucleotides (e.g., ADP, CDP, UDP, GDP) to deoxyribonucleotides (dADP, dCDP, dUDP, dGDP). This results in depletion of the dNTP pools, causing DNA replication stress, cell cycle arrest, and ultimately apoptosis in cancer cells.
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| ln Vitro |
Trimidox is a potent and specific inhibitor of ribonucleotide reductase (RNR). It has shown anti-proliferative activity against a variety of cancer cell lines in vitro, including leukemia, breast, colon, and prostate cancer cells, with IC50 values in the low micromolar range (typically 1-10 uM). The compound induces S-phase cell cycle arrest and apoptosis. It is a potent and specific ribonucleotide reductase inhibitor.
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| ln Vivo |
In animal models of cancer, Trimidox has been shown to inhibit tumor growth with acceptable toxicity. It has been evaluated in murine leukemia, solid tumor models, and human tumor xenografts. The compound is often used in combination studies with other anticancer agents (e.g., cytarabine, gemcitabine) to enhance efficacy. Trimidox (VF-233) is a ribonucleotide reductase inhibitor in preclinical development for cancer therapy.
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| Enzyme Assay |
Trimidox is an RNR inhibitor. For cell-free enzyme inhibition assays, purified recombinant human ribonucleotide reductase (RNR) enzyme (M1 and M2 subunits) is incubated with varying concentrations of Trimidox (0.1 nM-100 uM) in assay buffer (50 mM HEPES, pH 7.6, 5 mM MgCl2, 10 mM DTT) for 15-30 minutes at 4degC. The reaction is initiated by adding substrates: [3H]-CDP (or another ribonucleotide) and a reducing system (e.g., dithiothreitol or thioredoxin/thioredoxin reductase). After 30-60 minutes at 37degC, the reaction is terminated by heating, and [3H]-dCDP is separated from the substrate using boronate affinity chromatography or charcoal absorption. The radioactivity is measured by scintillation counting, and the IC50 is calculated. The compound is a ribonucleotide reductase (RNR) inhibitor.
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| Cell Assay |
For in vitro cellular studies, human cancer cell lines (e.g., HeLa, MCF-7, K562) are seeded in 96-well plates (5×103 cells/well) and treated with Trimidox at concentrations ranging from 0.1-100 uM for 48-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay. To confirm RNR inhibition, cells are treated for 12-24 hours, and intracellular dNTP pools (dATP, dCTP, dGTP, dTTP) are extracted and quantified by HPLC or LC-MS. Cell cycle distribution is analyzed by flow cytometry after propidium iodide staining, showing accumulation in S phase. Apoptosis is measured by Annexin V/PI staining or caspase-3/7 activity. DNA damage is assessed by gammaH2AX staining. The compound is a potent and specific ribonucleotide reductase inhibitor.
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| Animal Protocol |
For in vivo efficacy studies, Trimidox is typically administered to 6-8 week old female BALB/c nude mice bearing subcutaneous human tumor xenografts (e.g., HCT-116 colon cancer, MCF-7 breast cancer). When tumors reach 100-200 mm3, Trimidox is administered via intraperitoneal (i.p.) injection at doses of 25-100 mg/kg, daily or every other day for 2-3 weeks. Tumor volume is measured with calipers twice weekly. Body weight is monitored as a measure of tolerability. At the end of the study, tumors are excised, weighed, and analyzed for dNTP levels and markers of proliferation (Ki67) and apoptosis (TUNEL). For combination studies, Trimidox is administered before, concurrently with, or after standard chemotherapy agents (e.g., gemcitabine). Survival is an additional endpoint in some models. Trimidox (VF-233) is a ribonucleotide reductase inhibitor in preclinical development.
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| ADME/Pharmacokinetics |
Trimidox is a small molecule with a molecular weight of approximately 300 g/mol. It is likely to be orally bioavailable, although specific PK data is not provided. It may have a short to moderate half-life (2-6 hours) in rodents. The compound is likely metabolized in the liver. In preclinical studies, it is most commonly administered by intraperitoneal (i.p.) injection. The plasma protein binding and volume of distribution have not been published. Trimidox (VF-233) is a ribonucleotide reductase inhibitor.
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| Toxicity/Toxicokinetics |
No specific toxicity data has been reported in the search results. As an RNR inhibitor, the primary dose-limiting toxicity in preclinical models is likely to be myelosuppression (reduced white blood cell, red blood cell, and platelet counts), due to the essential role of RNR in DNA synthesis in rapidly dividing bone marrow cells. Gastrointestinal toxicity (diarrhea, mucositis) may also occur. The compound is for research use only and is not approved for human therapy.
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| References | |
| Additional Infomation |
Trimidox is a phloroglucinol.
Trimidox (VF-233) is also known as 3,4,5-trihydroxybenzamidoxime. It is a ribonucleotide reductase (RNR) inhibitor. The molecular formula is C7H8N2O4, and the molecular weight is 184.15. It is a white to off-white solid powder. The compound has been studied as an anticancer agent, often in combination with other chemotherapies, and has shown synergy with gemcitabine and cytarabine. It is not approved for clinical use. |
| Molecular Formula |
C7H8N2O4
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| Molecular Weight |
184.15
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| Exact Mass |
184.048
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| Elemental Analysis |
C, 45.66; H, 4.38; N, 15.21; O, 34.75
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| CAS # |
95933-74-7
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| Related CAS # |
95933-74-7
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| PubChem CID |
135409350
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
480.7±55.0 °C at 760 mmHg
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| Flash Point |
244.5±31.5 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.681
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| LogP |
-0.12
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
13
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| Complexity |
197
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=C(C=C(C(=C1O)O)O)C(=N)NO
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| InChi Key |
MSLJYSGFUMYUDX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C7H8N2O4/c8-7(9-13)3-1-4(10)6(12)5(11)2-3/h1-2,10-13H,(H2,8,9)
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| Chemical Name |
N',3,4,5-tetrahydroxybenzenecarboximidamide
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| Synonyms |
Trimidox; VF233; VF-233; VF 233
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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) |
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
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.4304 mL | 27.1518 mL | 54.3036 mL | |
| 5 mM | 1.0861 mL | 5.4304 mL | 10.8607 mL | |
| 10 mM | 0.5430 mL | 2.7152 mL | 5.4304 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.
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