Trimetrexate glucuronate (NSC 352122) is a folate antagonist that can inhibit dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylate, affecting DNA and RNA synthesis. It has potential anti-tumor activity and can also be used to inhibit Pneumocystis pneumonia.

Physicochemical Properties

Molecular Formula	C19H23N5O3.C6H10O7
Molecular Weight	563.55702
Exact Mass	563.223
CAS #	82952-64-5
Related CAS #	Trimetrexate;52128-35-5
PubChem CID	54949
Appearance	Off-white to light yellow solid powder
Density	1.305 g/cm3
Boiling Point	647ºC at 760 mmHg
Flash Point	345.1ºC
LogP	0.846
Hydrogen Bond Donor Count	8
Hydrogen Bond Acceptor Count	15
Rotatable Bond Count	11
Heavy Atom Count	40
Complexity	648
Defined Atom Stereocenter Count	4
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
InChi Key	ZCJXQWYMBJYJNB-LRDBBFHQSA-N
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
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
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	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].
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].
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%).
References	[1]. Biochemical pharmacology of the lipophilic antifolate, trimetrexate. Adv Enzyme Regul. 1984;22:187-206. [2]. Trimetrexate glucuronate associated with anti-Kaposi sarcoma effect. AIDS Patient Care STDS. 1996 Oct;10(5):280-1.
Additional Infomation	Trimetrexate Glucuronate can cause developmental toxicity according to state or federal government labeling requirements. Trimetrexate Glucuronate is a lipid soluble methotrexate derivative with potential antineoplastic activity. Trimetrexate glucuronate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylate, with subsequent inhibition of DNA and RNA synthesis. Trimetrexate glucuronate also exhibits antiviral activity. (NCI04)

Solubility Data

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

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	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.