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| Targets |
Cletoquine targets the same molecular pathways as hydroxychloroquine, including the heme polymerase in malaria parasites and the toll-like receptors (TLRs) in mammalian cells. In malaria parasites, cletoquine accumulates in the acidic food vacuole and inhibits the polymerization of heme, leading to the accumulation of toxic heme and parasite death. In mammalian cells, cletoquine inhibits TLR signaling, reducing the production of pro-inflammatory cytokines. The compound's immunomodulatory effects are mediated by the inhibition of TLR7 and TLR9 signaling.
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| ln Vitro |
In vitro, Cletoquine has been shown to possess antimalarial activity against Plasmodium falciparum, although it is less potent than hydroxychloroquine. The compound also exhibits immunomodulatory effects, inhibiting TLR7- and TLR9-mediated cytokine production in immune cells. In cell-based assays, cletoquine inhibits the production of IFN-α and TNF-α by plasmacytoid dendritic cells and monocytes. These in vitro findings are consistent with the pharmacological profile of hydroxychloroquine.
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| ln Vivo |
In order to measure the amount of chlorotoquine (desethylhydroxychloroquine) in the blood and tissues of BALB/c mice, hydroxychloroquine (5 mg/kg) was intravenously given. It can be inferred that tissues collect chlorotoquine when the tissue to blood concentration ratio (Kp) is less than 1. Liver (114.3), kidney (24.4), spleen (19.3), lung (16.5), heart (5.5) are the tissues with the highest and lowest chlorotoquine Kp ratios, respectively [3].
In vivo, Cletoquine contributes to the antimalarial and immunomodulatory effects of hydroxychloroquine. The compound's levels in plasma and tissues are used as a biomarker for hydroxychloroquine exposure and adherence to therapy. In patients with rheumatoid arthritis and systemic lupus erythematosus, cletoquine contributes to the therapeutic effects of hydroxychloroquine, although its role is less well-defined than that of the parent compound. |
| Enzyme Assay |
In vitro enzyme assays for Cletoquine are used to study its formation from hydroxychloroquine by cytochrome P450 enzymes. The assay is performed using human liver microsomes or recombinant CYP enzymes, with hydroxychloroquine as the substrate. The reaction is carried out in a buffer containing NADPH, and the formation of cletoquine is quantified by HPLC or LC-MS. The enzyme kinetics, including Vmax and Km, are calculated from the concentration-response curves.
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| Cell Assay |
In vitro cellular experiments for Cletoquine are performed using immune cells, such as peripheral blood mononuclear cells or plasmacytoid dendritic cells. Cells are treated with varying concentrations of the compound, and the inhibition of TLR-mediated cytokine production is assessed by ELISA or multiplex bead-based assays. The compound's effects on cell viability and proliferation are also assessed. These experiments are essential for characterizing the immunomodulatory activity of cletoquine.
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| Animal Protocol |
In vivo animal studies for Cletoquine involve measuring its levels in plasma and tissues following hydroxychloroquine administration. The compound is extracted from biological samples and analyzed by LC-MS. Its levels are used as a biomarker for hydroxychloroquine metabolism and exposure. Studies in animal models of malaria and autoimmune diseases have investigated the role of cletoquine in the therapeutic and toxic effects of hydroxychloroquine.
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| ADME/Pharmacokinetics |
Cletoquine is a metabolite of hydroxychloroquine, and its pharmacokinetic properties are closely linked to those of the parent compound. The formation of cletoquine from hydroxychloroquine occurs primarily in the liver, and the metabolite has a similar half-life to hydroxychloroquine, approximately 1-2 months. The compound is extensively distributed in tissues and is slowly eliminated from the body. Its pharmacokinetic profile contributes to the long-acting effects of hydroxychloroquine.
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| Toxicity/Toxicokinetics |
The toxicity of Cletoquine is similar to that of hydroxychloroquine, although it is generally considered to be less toxic. Common adverse effects include gastrointestinal disturbances, headache, and visual disturbances. Prolonged use of hydroxychloroquine and its metabolites can lead to retinopathy and other serious adverse effects. The safety profile of cletoquine is an important consideration in the use of hydroxychloroquine for chronic conditions such as rheumatoid arthritis and lupus.
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| References |
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| Additional Infomation |
Cletoquine is the active metabolite of hydroxychloroquine, formed by deethylation in the liver. It retains significant antimalarial and immunomodulatory activity and contributes to the therapeutic effects of hydroxychloroquine. Cletoquine is used as a biomarker for hydroxychloroquine exposure and as a reference standard in pharmacokinetic studies. Its formation and elimination are important considerations in the clinical use of hydroxychloroquine for malaria, rheumatoid arthritis, and systemic lupus erythematosus.
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| Molecular Formula |
C16H22N3OCL
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|---|---|
| Molecular Weight |
307.81838
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| Exact Mass |
307.145
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| CAS # |
4298-15-1
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| Related CAS # |
Cletoquine oxalate;14142-64-4;Cletoquine-d4-1;1216461-56-1;Cletoquine-d4;1854126-47-8
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| PubChem CID |
71826
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.212 g/cm3
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| Boiling Point |
514.7ºC at 760 mmHg
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| Flash Point |
265.1ºC
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| Index of Refraction |
1.623
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| LogP |
3.514
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
21
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| Complexity |
293
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=C2C(C(NC(C)CCCNCCO)=CC=N2)=CC=1
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| InChi Key |
XFICNUNWUREFDP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H22ClN3O/c1-12(3-2-7-18-9-10-21)20-15-6-8-19-16-11-13(17)4-5-14(15)16/h4-6,8,11-12,18,21H,2-3,7,9-10H2,1H3,(H,19,20)
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| Chemical Name |
2-[4-[(7-chloroquinolin-4-yl)amino]pentylamino]ethanol
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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 | 3.2487 mL | 16.2433 mL | 32.4865 mL | |
| 5 mM | 0.6497 mL | 3.2487 mL | 6.4973 mL | |
| 10 mM | 0.3249 mL | 1.6243 mL | 3.2487 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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