| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
metabolite of trimethoprim
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|---|---|
| ln Vitro |
The main metabolite of trimethoprim is trimethoprim 3-oxide[1]. In human liver microsomes (HLMs), CYP1A1 and CYP1B1 convert trimethoprim 3-oxide (3-NO-TMP) at the highest rates from trimethoprim. Trimethoprim 3-oxide synthesis is inhibited by the CYP1A inhibitor α-Naphthoflavone, while other competing P450 inhibitors do not clearly reduce its formation[1].
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| References |
[1]. Goldman JL, et al. In Vitro Hepatic Oxidative Biotransformation of Trimethoprim. Drug Metab Dispos. 2015 Sep;43(9):1372-80.
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| Additional Infomation |
Since the 1960s, trimethoprim (TMP) has been widely used, both alone and in combination with sulfamethoxazole. However, information on the role of cytochrome P450 enzymes (P450) in the formation of TMP primary metabolites is scarce. Therefore, we conducted in vitro studies to identify and more comprehensively characterize the P450 that catalyzes the formation of six TMP primary metabolites: TMP 1-N-oxide (1-NO-TMP) and 3-N-oxide (3-NO-TMP), 3'- and 4'-demethyl-TMP, benzyl alcohol (Cα-OH-TMP), and the N-acetylcysteine (NAC) adduct of TMP (Cα-NAC-TMP). In human liver microsomes (HLM), the formation kinetics of each TMP metabolite conformed to single-enzyme Michaelis kinetics, and the Km values were significantly higher (≥10-fold) than at therapeutic concentrations of TMP (50 µM). A correlation study was conducted on the generation rates of a series of metabolites in HLMs and their association with labeled P450 activity. Inhibition studies using selective P450 inhibitors and mixed HLM incubation were also performed. The results showed that 1-NO-TMP, Cα-NAC-TMP, and Cα-OH-TMP are primarily generated by CYP3A4. Conversely, 3-NO-TMP is mainly generated by CYP1A2 in HLMs and can be inhibited by α-naphthylflavonoids. 4'-Demethyl-TMP is considered an active metabolic precursor of TMP, generated by various P450 enzymes (including CYP3A4). Its activity is correlated with the activity of various P450 enzymes, but it is mainly inhibited by ketoconazole (with an inhibition rate as high as 50%), indicating that CYP3A4 plays a major role in the 4'-demethylation of TMP. The 3'-demethylation of TMP is catalyzed by a variety of P450 enzymes, including CYP2C9, and its activity is related to that of CYP2C9 enzymes and is inhibited by sulfadiazine (with an inhibition rate of up to 40%). Overall, CYP2C9 and CYP3A4 appear to be the main contributors to the primary metabolism of TMP. [1]
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| Molecular Formula |
C14H18N4O4
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|---|---|
| Molecular Weight |
306.32
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| Exact Mass |
306.133
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| CAS # |
27653-67-4
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| PubChem CID |
23278278
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| Appearance |
Typically exists as White to off-white solid at room temperature
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| LogP |
1.479
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
22
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| Complexity |
466
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| Defined Atom Stereocenter Count |
0
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| SMILES |
NC1=NC=C(CC2=CC(OC)=C(OC)C(OC)=C2)C(N)=[N+]1[O-]
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| InChi Key |
YQVPBGLBUGARPD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H18N4O4/c1-20-10-5-8(6-11(21-2)12(10)22-3)4-9-7-17-14(16)18(19)13(9)15/h5-7,16,19H,4,15H2,1-3H3
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| Chemical Name |
3-hydroxy-2-imino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-4-amine
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| Synonyms |
27653-67-4; Trimethoprim 3-oxide; 2,4-Pyrimidinediamine, 5-[(3,4,5-trimethoxyphenyl)methyl]-, 3-oxide; Trimethoprim 3-N-oxide; 3-NO-Trimethoprim; NVW7CIX03F; 3-hydroxy-2-imino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-4-amine; Trimethoprim 3-oxide (Trimethoprim 3-N-oxide);
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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 | 3.2646 mL | 16.3228 mL | 32.6456 mL | |
| 5 mM | 0.6529 mL | 3.2646 mL | 6.5291 mL | |
| 10 mM | 0.3265 mL | 1.6323 mL | 3.2646 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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