| Size | Price | |
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| 1mg | ||
| Other Sizes |
| Targets |
Plasmodium
Proguanil-d6 is a labeled version of Proguanil. The parent compound, Proguanil, is a prophylactic antimalarial agent that is metabolized in the body to its active form, Cycloguanil, primarily by the cytochrome P450 enzyme CYP2C19. Cycloguanil is a dihydrofolate reductase (DHFR) inhibitor, which is the therapeutic target, and the labeling does not alter this mechanism. |
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| ln Vitro |
Proguanil-d6 is the deuterium-labeled Proguanil, which is a prophylactic antimalarial agent. The parent compound, Proguanil, is a prodrug that is converted to its active metabolite, Cycloguanil. The deuterated version is used largely as a tracer for quantitation during the drug development process, and the substitution may influence the pharmacokinetic profile.
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| ln Vivo |
Proguanil-d6 is used as an analytical standard and is not administered in vivo. However, its non-deuterated parent, Proguanil, is an antimalarial agent that is active in vivo after metabolic conversion to Cycloguanil, which inhibits parasite dihydrofolate reductase (DHFR), thereby blocking DNA synthesis in the malaria parasite.
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| Enzyme Assay |
A cell-free DHFR inhibition assay is used for the active metabolite. The enzyme (Plasmodium falciparum DHFR) is incubated with dihydrofolate and NADPH in the presence of the test compound. The decrease in absorbance at 340 nm is monitored. The IC50 is calculated from the dose-response curve. Proguanil itself is inactive in this assay.
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| Cell Assay |
Proguanil-d6 is not used in cell-based assays. However, its non-deuterated parent, Proguanil, can be tested in vitro against P. falciparum. Parasites are cultured in human erythrocytes in RPMI-1640 medium. Various concentrations of Proguanil are added, and after 48-72 hours, parasite growth is measured by [3H]-hypoxanthine incorporation or by microscopy after Giemsa staining.
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| Animal Protocol |
Proguanil-d6 is used as an internal standard for PK studies. A standard animal protocol: male CD-1 mice (20-25g) are administered a single oral dose of Proguanil (20 mg/kg). Blood samples are collected via tail vein at various times. Plasma is processed and analyzed by LC-MS/MS using Proguanil-d6 as an internal standard to quantify Proguanil and Cycloguanil levels.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Proguanil-d6 are expected to be nearly identical to those of the non-deuterated Proguanil. Proguanil is well absorbed orally, with a Tmax of 2-4 hours in humans. It is metabolized by CYP2C19 to its active metabolite, Cycloguanil. The elimination half-life of Proguanil is approximately 12-20 hours.
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| Toxicity/Toxicokinetics |
The safety profile of Proguanil-d6 is expected to be similar to its non-deuterated parent. Proguanil is generally well-tolerated. The most common side effects include mouth ulcers and gastrointestinal disturbances. Rare but serious adverse effects include severe hypoglycemia. The deuterated version is used in trace amounts as an analytical standard.
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| Additional Infomation |
Proguanil-d6 is a research-grade stable isotope-labeled compound, not an approved drug. It is the deuterium labeled Proguanil, which is a prophylactic antimalarial agent. This product is for research use only and is not intended for human therapeutic applications. It is a valuable tool for LC-MS/MS method development and drug metabolism studies.
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| Molecular Formula |
C11H10D6CLN5
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|---|---|
| Related CAS # |
Proguanil;500-92-5;Proguanil hydrochloride;637-32-1
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| Appearance |
Typically exists as solid at room temperature
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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.) |
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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