| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Dihydrofolate reductase; Influenza A virus
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|---|---|
| ln Vitro |
By preventing dihydrofolate reductase (DHFR) from functioning, trimethoprim disrupts the metabolism of folate and converts dihydrofolate to tetrahydrofolate (THF) [1]. In E. coli, trimethoprim (3 μg/mL; 1 h) causes significant heat shock proteins (Hsps) and protein aggregation. coli cells, indicating that protein misfolding is brought on by trimethoprim sulfate [1]. E. coli produces DnaK, DnaJ, GroEL, ClpB, and IbpA/B Hsps when treated with trimethoprim (1.5–3 μg/mL; 1 hour). Coli cells subjected to heat stress and folate [1].
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| ln Vivo |
Trimethoprim (10 mg/kg; IV; every 12 hours; 3 days) demonstrated antibacterial activity against Neisseria meningitidis, Escherichia coli, Haemophilus influenzae, and Streptococcus pneumoniae in infected mice[2]. Trimethoprim has a half-life of about an hour in full serum and a MIC value of about 1 μM against E. coli. It can be associated with thiomaltose (TM-TMP) and shows stability. Coli [2]. The injection of trimethoprim-zinc mixed suspension (10 mg/mL; 0.5 mL) lowers virus titers and increases the survival rate of chicken embryos [4].
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| Enzyme Assay |
Influenza virus was isolated from patients and propagated in eggs. We determined viral load that infects 50% of eggs (50% egg lethal dose, ELD50). We introduced 10 ELD50 into embryonated eggs and repeated the experiments using 100 ELD50. A mixture of zinc oxide (Zn) and trimethoprim (TMP) (weight/weight ratios ranged from 0.01 to 0.3, Zn/TMP with increment of 0.1) was tested for embryo survival of the infection (n = 12 per ratio, in triplicates). Embryo survival was determined by candling eggs daily for 7 days. Controls of Zn, TMP, saline or convalescent serum were conducted in parallel. The effect of Tri-Z on virus binding to its cell surface receptor was evaluated in a hemagglutination inhibition (HAI) assay using chicken red cells. Tri-Z was prepared to concentration of 10 mg TMP and 1.8 mg Zn per ml, then serial dilutions were made. HAI effect was expressed as scores where ++++ = no effect; 0 = complete HAI effect.
Results: TMP, Zn or saline separately had no effect on embryo survival, none of the embryos survived influenza virus infection. All embryos treated with convalescent serum survived. Tri-Z, at ratio range of 0.15-0.2 (optimal ratio of 0.18) Zn/TMP, enabled embryos to survive influenza virus despite increasing viral load (> 80% survival at optimal ratio). At concentration of 15 µg/ml of optimal ratio, Tri-Z had total HAI effect (scored 0). However, at clinical concentration of 5 µg/ml, Tri-Z had partial HAI effect (+ +). Conclusion: Acting on host cells, Tri-Z at optimal ratio can reduce the lethal effect of influenza A virus in chick embryo. Tri-Z has HAI effect. These findings suggest that combination of trimethoprim and zinc at optimal ratio can be provided as treatment for influenza and possibly other respiratory RNA viruses infection in man.[1] |
| Cell Assay |
Trimethoprim (TMP), an inhibitor of dihydrofolate reductase, decreases the level of tetrahydrofolate supplying one-carbon units for biosynthesis of nucleotides, proteins, and panthotenate. We have demonstrated for the first time that one of the effects of the TMP action in E. coli cells is protein aggregation and induction of heat shock proteins (Hsps). TMP caused induction of DnaK, DnaJ, GroEL, ClpB, and IbpA/B Hsps. Among these Hsps, IbpA/B were most efficiently induced by TMP and coaggregated with the insoluble proteins. Upon folate stress, deletion of the delta ibpA/B operon resulted in increased protein aggregation but did not influence cell viability.[1]
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| Animal Protocol |
Animal/Disease Models: Female C3H/HeOuJ mice (transurethral infection in 50 μL suspension containing 1-2×107 CFU E. coli under 3% isoflurane) [2]
Doses: 10 mg/kg Route of Administration: intravenous (iv) (iv)injection ; Once every 12 hrs (hrs (hours)); 3 days Experimental Results:Antibacterial activity against Haemophilus influenzae, Streptococcus pneumoniae, Escherichia coli and Neisseria meningitidis. The CD50 of the infected person was 150 mg/kg, 335 mg/kg, 27.5 respectively. mg/kg and 8.4 mg/kg mice. Animal/Disease Models: Fertilized eggs (H3N2 virus is injected into the amniotic membrane and allantoic cavity on day 8) [4] Doses: 10 mg/mL; 0.5 mL Route of Administration: Trimethoprim-zinc composite suspension is injected into the air sac; single dose Experimental Results: The virus titer was diminished and the survival rate of chicken embryos was improved. Survival rates peaked at a ratio of approximately 0.18 (Zn/trimethoprim). |
| References |
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| Additional Infomation |
Trimethoprim Sulfate is the sulfate salt form of trimethoprim, a synthetic substituted pyrimidine with antibacterial activity. Trimethoprim sulfate selectively binds to and reversibly inhibits dihydrofolate reductase, thereby blocking the production of tetrahydrofolic acid from dihydrofolic acid. This leads to an inhibition of bacterial synthesis of folic acid, thereby affecting nucleic acid and protein synthesis. Trimethoprim sulfate has a stronger binding affinity for the bacterial enzyme than for the corresponding mammalian enzyme.
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| Molecular Formula |
2[C14H18N4O3].H2O4S
|
|---|---|
| Molecular Weight |
678.71392
|
| Exact Mass |
678.243
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| Elemental Analysis |
C, 49.55; H, 5.64; N, 16.51; O, 23.57; S, 4.72
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| CAS # |
56585-33-2
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| Related CAS # |
Trimethoprim;738-70-5;Trimethoprim lactate;23256-42-0;Trimethoprim-d3;1189923-38-3;Trimethoprim hydrochloride;60834-30-2;Trimethoprim-13C3;1189970-95-3; 56585-33-2 (sulfate)
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| PubChem CID |
64936
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.663
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
18
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| Rotatable Bond Count |
10
|
| Heavy Atom Count |
47
|
| Complexity |
388
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C(=CC(=C1)CC2=CNC(=N)NC2=N)OC)OC.COC1=C(C(=CC(=C1)CC2=CNC(=N)NC2=N)OC)OC.OS(=O)(=O)O
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| InChi Key |
UILMMYFRNCCPLK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/2C14H18N4O3.H2O4S/c2*1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15;1-5(2,3)4/h2*5-7H,4H2,1-3H3,(H4,15,16,17,18);(H2,1,2,3,4)
|
| Chemical Name |
sulfuric acid;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine
|
| Synonyms |
Trimethoprim sulfate; 56585-33-2; BW 72U; Trimethoprim sulphate; E377MF8EQ8; Trimethoprim sulfate [USAN:USP]; BW-72U; sulfuric acid;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine;
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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 | 1.4734 mL | 7.3669 mL | 14.7338 mL | |
| 5 mM | 0.2947 mL | 1.4734 mL | 2.9468 mL | |
| 10 mM | 0.1473 mL | 0.7367 mL | 1.4734 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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