| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Dihydrofolate reductase (DHFR) (IC₅₀: 0.03–0.1 μM in Plasmodium falciparum)
|
|---|---|
| ln Vitro |
- Malaria parasite growth inhibition: Chlorproguanil (0.01–10 μM) demonstrated dose-dependent inhibition of P. falciparum growth in culture, with EC₅₀ values correlating with DHFR inhibition. Synergy was observed when combined with dapsone (FICI 0.4–0.6)[5,6].
- DHFR enzyme inhibition: Recombinant P. falciparum DHFR was potently inhibited by Chlorproguanil (IC₅₀: 0.03 μM), blocking tetrahydrofolate synthesis and disrupting parasite DNA replication[6].
|
| ln Vivo |
- Malaria prophylaxis in children: Oral Chlorproguanil (1.2 mg/kg) + dapsone (2.4 mg/kg) reduced spleen rates and parasite density in Gambian children over 3 years of administration. However, it showed less efficacy than pyrimethamine/sulfadoxine in reducing febrile episodes[5].
- Treatment of uncomplicated malaria: Three-dose Chlorproguanil (2 mg/kg) + dapsone regimen achieved 70–80% parasite clearance by day 7 in African patients, with reduced treatment failure compared to sulfadoxine/pyrimethamine[6].
|
| Enzyme Assay |
DHFR activity assay: Recombinant P. falciparum DHFR was incubated with Chlorproguanil (0.01–10 μM) and NADPH. Dihydrofolate addition initiated the reaction, and product formation was measured spectrophotometrically at 340 nm. IC₅₀ was determined by nonlinear regression[6].
|
| Cell Assay |
Parasite growth inhibition: Synchronized P. falciparum cultures treated with Chlorproguanil (0.01–10 μM) showed reduced [³H]hypoxanthine incorporation after 48 hours, reflecting decreased nucleic acid synthesis[6].
|
| Animal Protocol |
Rodent malaria model: Mice infected with P. berghei received oral Chlorproguanil (10–20 mg/kg/day). Survival rates and parasitemia were monitored. Combination with dapsone (5–10 mg/kg) enhanced protective efficacy[10].
|
| ADME/Pharmacokinetics |
Absorption: The time to peak concentration (Tmax) of oral chlorproguanidine (100 mg) is 2-4 hours, and the bioavailability is 60-70%. Food can increase Cmax by 20-30% [7]. Metabolism: It is mainly metabolized in the liver by CYP2C19 to the active metabolite cyclic guanidine (t₁/₂: 16-20 hours). Half-life of the parent drug: 14-16 hours [7]. Excretion: Approximately 60% is excreted in the urine as metabolites, and 30% is excreted in the feces. Less than 5% of the parent drug is detected [7].
|
| Toxicity/Toxicokinetics |
Acute toxicity: LD₅₀ >2000 mg/kg (oral) in rats. Common adverse reactions include gastrointestinal disturbances and reversible hematological changes [6,16]. - Hematological effects: In vitro studies have shown that chlorpromazine (520 ng/mL) induces dose-dependent DNA damage in human lymphocytes without affecting cell viability [16].
13956122 Oral LD50 in mice: 100 mg/kg British Journal of Pharmacology and Chemotherapy, 5(438), 1950 [PMID:14777868] 13956122 Intraperitoneal LD50 in mice: 25 mg/kg British Journal of Pharmacology and Chemotherapy, 5(438), 1950 [PMID:14777868] 13956122 Intravenous LD50 in mice: 25 mg/kg British Journal of Pharmacology and Chemotherapy, 5(438), 1950 [PMID:14777868] |
| References | |
| Additional Infomation |
- Mechanism of action: Chlorprothioguanidine is a prodrug that can be converted to cyclic guanidine, which inhibits dihydrofolate reductase (DHFR). Synergistic effects with dapsone involve dual inhibition of folate metabolism [5,6]. - Resistance: Point mutations in the DHFR of Plasmodium falciparum (e.g., C59R, S108N) confer resistance. Cross-resistance with pyrimethamine is common [6]. - Clinical use: It has been approved in combination with dapsone for the prevention and treatment of malaria in areas resistant to sulfadoxine/pyrimethamine [5,6].
|
| Molecular Formula |
C11H16CL3N5
|
|---|---|
| Molecular Weight |
324.64
|
| CAS # |
6001-93-0
|
| Related CAS # |
537-21-3;Parent
|
| PubChem CID |
13956122
|
| Appearance |
Typically exists as solids at room temperature
|
| LogP |
4.719
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
1
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
19
|
| Complexity |
329
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)NC(=N)NC(=N)NC1=CC(=C(C=C1)Cl)Cl.Cl
|
| Synonyms |
Chlorproguanil hydrochloride; Lapudrine; Chlorproguanil HCl; 6001-93-0; Chloroproguanil monohydrochloride; EINECS 227-846-5; UNII-6T04V14CU9; 6T04V14CU9;
|
| 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)
|
| 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
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 | 3.0803 mL | 15.4017 mL | 30.8034 mL | |
| 5 mM | 0.6161 mL | 3.0803 mL | 6.1607 mL | |
| 10 mM | 0.3080 mL | 1.5402 mL | 3.0803 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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