| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
Dihydrofolate reductase (DHFR); folate metabolism; purine and thymidylate synthesis.
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|---|---|
| ln Vitro |
In human lymphoblastoid cells, WI-L2 cells treated with trimethoxylate glucuronate (0.05–1 μM) for six hours show a decrease in adenylate and guanylate, but pyrimidine nucleotides, such as CTP and UTP, show a significant dose-dependent increase [1]. In L1210 mouse leukemia cells, trimethroxate glucuronate (1 μM, 2 h) can decrease dTTP levels by 29% while also decreasing dGTP and dATP. Additionally, it can broadly prevent deoxyuridine from being incorporated into DNA [1].
Trimetrexate glucuronate inhibits DHFR with high potency: ID50 values of 26.1 nM for P. jirovecii DHFR and 1.4 nM for T. gondii DHFR. In RFC-deficient cells, it is >4,000-fold more cytotoxic than methotrexate (IC50 0.059 μM vs 251 μM). It is a potent inhibitor of human DHFR and retains activity in methotrexate-resistant cell lines. |
| ln Vivo |
Inbred DBA/2 mice with L1210 leukemia respond well to trimethoxyxate glucuronate (ip, 100-225 mg/kg daily, days 1, 5, and 9) in terms of antitumor activity [1].
In vivo, trimetrexate glucuronate is administered intravenously for P. jirovecii pneumonia, often with leucovorin rescue to protect host tissues. It achieves therapeutic concentrations in lung tissue and is effective in immunocompromised patients. Its lipophilic nature allows broad tissue distribution, including penetration into the central nervous system. |
| Enzyme Assay |
For DHFR assays, purified DHFR is incubated with dihydrofolate, NADPH, and serially diluted trimetrexate. NADPH oxidation is monitored at 340 nm, and IC50 is derived from dose-response curves. Selectivity is assessed against DHFR from different species.
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| Cell Assay |
For cell-based assays, cancer cells or P. jirovecii are treated with trimetrexate (0.1 nM–10 μM) for 24–72 h. Viability is measured by MTT or a fluorescence-based proliferation assay. Thymidylate synthesis is assessed by [³H]thymidine incorporation, and apoptosis is measured by Annexin V/PI.
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| Animal Protocol |
Animal/Disease Models: Inbred DBA/2 mice with L1210 leukemia [1]
Doses: 100, 150, 225 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; results on days 1, 5, and 9: maximum lifespan shown T/C value is 171%. Animal/Disease Models: M5076 tumor C57BL/6 mice [1] Doses: 38, 62 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; 1-9 days Experimental Results: demonstrated toxicity at the high dose of 62 mg/kg (>10% early death) and demonstrated no activity at the low dose of 38 mg/kg (lifetime T/C <130%). For in vivo studies, immunosuppressed rats or mice with P. jirovecii pneumonia receive trimetrexate glucuronate (e.g., 1–20 mg/kg/day, i.v.) with leucovorin rescue for 7–21 days. Lung pathogen burden is quantified by microscopy or PCR, and survival is monitored. Plasma drug concentrations are measured by LC-MS/MS. |
| References | |
| Additional Infomation |
Trimetrexate glucuronide may cause developmental toxicity, depending on state or federal labeling requirements. Trimetrexate glucuronide is a lipid-soluble methotrexate derivative with potential antitumor activity. It inhibits dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidine nucleotides, and consequently inhibiting DNA and RNA synthesis. Trimetrexate glucuronide also possesses antiviral activity. (NCI04)
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| Molecular Formula |
C19H23N5O3.C6H10O7
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|---|---|
| Molecular Weight |
563.55702
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| Exact Mass |
563.223
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| CAS # |
82952-64-5
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| Related CAS # |
Trimetrexate;52128-35-5
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| PubChem CID |
54949
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.305 g/cm3
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| Boiling Point |
647ºC at 760 mmHg
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| Flash Point |
345.1ºC
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| LogP |
0.846
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
40
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| Complexity |
648
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC1=C(C=CC2=C1C(=NC(=N2)N)N)CNC3=CC(=C(C(=C3)OC)OC)OC.C(=O)[C@@H]([C@H]([C@@H]([C@@H](C(=O)O)O)O)O)O
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| InChi Key |
ZCJXQWYMBJYJNB-LRDBBFHQSA-N
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| InChi Code |
InChI=1S/C19H23N5O3.C6H10O7/c1-10-11(5-6-13-16(10)18(20)24-19(21)23-13)9-22-12-7-14(25-2)17(27-4)15(8-12)26-3;7-1-2(8)3(9)4(10)5(11)6(12)13/h5-8,22H,9H2,1-4H3,(H4,20,21,23,24);1-5,8-11H,(H,12,13)/t;2-,3+,4-,5-/m.0/s1
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| Chemical Name |
5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline-2,4-diamine;(2S,3S,4S,5R)-2,3,4,5-tetrahydroxy-6-oxohexanoic acid
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: ~100 mg/mL (~177.4 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.44 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: 2.5 mg/mL (4.44 mM) 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: 2.5 mg/mL (4.44 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. View More
Solubility in Formulation 4: 4 mg/mL (7.10 mM) in 50% PEG300 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. Solubility in Formulation 5: 2.5 mg/mL (4.44 mM) in 0.5% CMC/saline water (add these co-solvents sequentially from left to right, and one by one), Suspended solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O 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 | 1.7744 mL | 8.8722 mL | 17.7443 mL | |
| 5 mM | 0.3549 mL | 1.7744 mL | 3.5489 mL | |
| 10 mM | 0.1774 mL | 0.8872 mL | 1.7744 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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