| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Proguanil-d6 hydrochloride shares the same biological target as its non-deuterated parent compound. It is metabolized to Cycloguanil, a potent and selective inhibitor of parasite dihydrofolate reductase (DHFR). The deuterium labeling does not alter the mechanism of action but is used for analytical purposes. It targets dihydrofolate reductase (DHFR).
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
Proguanil-d6 hydrochloride is an antimalarial precursor that is metabolized to the active metabolite Cycloguanil. As a stable heavy isotope-labeled compound, it is largely used as a tracer for quantitation during drug development. The deuteration may affect the pharmacokinetic and metabolic profiles of the drug. |
| ln Vivo |
Proguanil-d6 hydrochloride is used as an analytical standard and is not intended for in vivo administration for therapeutic purposes. However, its non-deuterated parent, Proguanil, is an antimalarial prodrug that is activated in vivo to Cycloguanil, which exerts its antiparasitic effects by inhibiting parasite DHFR.
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| Enzyme Assay |
A cell-free DHFR enzyme inhibition assay is used to measure the activity of the active metabolite. The enzyme is incubated with dihydrofolate and NADPH in the presence of the test compound. The decrease in absorbance at 340 nm is measured. The IC50 is calculated from the concentration-response curve. Proguanil itself is inactive in this assay; it is converted to Cycloguanil.
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| Cell Assay |
Proguanil-d6 hydrochloride is not used in cell-based assays. However, its non-deuterated parent, Proguanil, can be used in cell-based assays to evaluate antimalarial activity. Plasmodium falciparum-infected erythrocytes are cultured in vitro and treated with various concentrations of the compound. Parasite growth is measured by [3H]-hypoxanthine incorporation or by microscopy.
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| Animal Protocol |
Proguanil-d6 hydrochloride is used as an internal standard for PK studies of Proguanil. A standard animal protocol: male SD rats (200-250g) are administered a single oral dose of Proguanil hydrochloride (10 mg/kg). Blood samples are collected at various time points. Plasma is processed and analyzed by LC-MS/MS using Proguanil-d6 as an internal standard.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Proguanil-d6 hydrochloride are expected to be nearly identical to those of the non-deuterated Proguanil hydrochloride. Proguanil is well absorbed orally and is metabolized primarily by CYP2C19 to its active metabolite, Cycloguanil. The elimination half-life of Proguanil in humans is 12-20 hours.
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| Toxicity/Toxicokinetics |
Proguanil hydrochloride, the non-deuterated parent, is generally well-tolerated. The most common adverse effects include mouth ulcers, hair loss, and gastrointestinal disturbances. Rare but serious adverse effects include severe hypoglycemia and hematological disorders. The deuterated version is used only in trace amounts as an analytical standard.
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| References |
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Pudney M, et al. Atovaquone and proguanil hydrochloride: a review of nonclinical studies. J Travel Med. 1999 May;6 Suppl 1:S8-12. [3]. Srivastava IK, et al. A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antimicrob Agents Chemother. 1999 Jun;43(6):1334-9. |
| Additional Infomation |
Proguanil-d6 hydrochloride is a stable isotope-labeled research compound, not an approved drug. It is used as an internal standard for the quantification of Proguanil. The parent compound, Proguanil, is a DHFR inhibitor and antimalarial agent. This product is for research use only and is not for human therapeutic applications.
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| Molecular Formula |
C11H11D6CL2N5
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|---|---|
| Related CAS # |
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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