| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
Piperaquine targets the heme detoxification pathway in the malaria parasite, similar to other quinoline antimalarials. It inhibits the formation of hemozoin, a crystalline pigment formed by the parasite to detoxify free heme released during hemoglobin digestion. By preventing this detoxification, the compound causes the accumulation of toxic heme, leading to oxidative damage and parasite death. It is also an inhibitor of autophagy.
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| ln Vitro |
In vitro, Piperaquine demonstrates potent antimalarial activity. It is highly active against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. The compound's efficacy is typically measured by its ability to inhibit parasite growth in cultured erythrocytes, with IC50 values in the nanomolar range. It is also used in research to study drug resistance mechanisms and to evaluate combination therapies.
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| ln Vivo |
In mice, piperaquine (10-90 mg/kg; single intraperitoneal injection) decreases parasitemia at all tested doses [1]. The piperaquine (90 mg/kg; single intraperitoneal injection) had the following t1/2, apparent clearance, and apparent volume of distribution: 17.8 days, 33.5 mg·h/L, 1.55 L/h/kg, and 956 L/kg, respectively; 16.1 days for healthy mice and 16.1 days for mice with malaria, 27.3 mg·h/L, 1.9 L/h/kg, and 1,059 L/kg[1].
In vivo, Piperaquine is a key component of the fixed-dose combination therapy dihydroartemisinin-piperaquine, which is recommended by the World Health Organization for the treatment of uncomplicated malaria. It has a long half-life, making it suitable for use in combination with short-acting artemisinin derivatives. The compound is also used in preclinical models to study its efficacy against malaria and to investigate drug resistance. |
| Enzyme Assay |
The in vitro antimalarial susceptibility assay for Piperaquine involves culturing P. falciparum in human erythrocytes in the presence of varying concentrations of the compound. Parasite growth is measured by assessing the incorporation of [3H]-hypoxanthine or by using a fluorescent dye such as SYBR Green I. The IC50 is calculated from the dose-response curve. The compound's activity against chloroquine-resistant strains is compared to that of chloroquine to assess cross-resistance patterns.
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| Cell Assay |
In vitro cell culture studies for Piperaquine are primarily conducted in P. falciparum cultures. To study its mechanism as an autophagy inhibitor, mammalian cell lines can be treated with the compound, and the accumulation of autophagosomes is monitored using fluorescence microscopy with LC3-GFP reporter constructs or by Western blotting for LC3-II. The compound's effect on cell viability in mammalian cells is also assessed to determine its selectivity index.
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| Animal Protocol |
Animal/Disease Models: Male balb/c (Bagg ALBino) mouse (7 to 8 weeks) inoculated with Plasmodium berghei parasites [1]
Doses: 0, 10, 30, 90 mg/kg Route of Administration: Single ip administration Experimental Results:Median Survival time is 10 days at a dose of 10 mg/kg. At the 30 mg/kg dose, the median survival time was 54 days. All mice were active, alert, and had stable weight throughout the study at 90 mg/kg. Animal/Disease Models: Male Swiss mice (6 weeks old) [1] Doses: 90 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Single intraperitonealadministration Experimental Results: t1/2=17.8 d; AUC=33.5 mg·h/L; apparent clearance rate=1.55L/h/kg; apparent volume of distribution=956L/kg. In vivo animal experiments for Piperaquine are performed in mouse models of malaria, such as the Plasmodium berghei or P. yoelii infection models. The compound is administered orally, and its efficacy is assessed by measuring the reduction in parasitemia over time. In combination studies, Piperaquine is co-administered with artemisinin derivatives to evaluate synergistic effects and to monitor the emergence of drug resistance. |
| ADME/Pharmacokinetics |
Piperaquine tetraphosphate tetrahydrate is soluble in water at 2 mg/mL (2.0 mM), but is insoluble in DMSO and ethanol. It is typically stored as a powder at room temperature, and stability testing shows it can be shipped without cooling. The compound is hygroscopic and should be protected from moisture. For in vivo studies, it is often formulated as a suspension in aqueous vehicles containing a surfactant.
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| Toxicity/Toxicokinetics |
Toxicological data for Piperaquine indicate that it is generally well-tolerated at therapeutic doses. Common side effects include gastrointestinal disturbances, headache, and dizziness. Cardiotoxicity, specifically QT interval prolongation, has been observed, which is a class effect of quinoline antimalarials. Preclinical studies have shown that it has a low potential for mutagenicity and carcinogenicity.
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| References |
[1]. Moore BR, et, al. Pharmacokinetics and pharmacodynamics of piperaquine in a murine malaria model. Antimicrob Agents Chemother. 2008 Jan; 52(1): 306-11.
[2]. Davis TME, et, al. Piperaquine: a resurgent antimalarial drug. Drugs. 2005; 65(1): 75-87. |
| Additional Infomation |
Piperaquine is an approved antimalarial drug, typically used in combination with dihydroartemisinin. It is included in the WHO Model List of Essential Medicines. The compound is also available as a research-grade chemical for antimalarial research and for studying drug resistance mechanisms. Its role as an autophagy inhibitor has also made it a subject of interest in cancer research.
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| Molecular Formula |
C29H52CL2N6O20P4
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| Molecular Weight |
999.552430152893
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| Exact Mass |
998.156
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| CAS # |
915967-82-7
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| Related CAS # |
Piperaquine phosphate;85547-56-4;Piperaquine tetraphosphate;911061-10-4;Piperaquine;4085-31-8
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| PubChem CID |
49849842
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| Appearance |
White to off-white solid powder
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| Melting Point |
252 °C(dec.)
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| LogP |
1.458
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| Hydrogen Bond Donor Count |
16
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| Hydrogen Bond Acceptor Count |
26
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
61
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| Complexity |
704
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=P(O)(O)O.ClC1C=C2N=CC=C(C2=CC=1)N1CCN(CCCN2CCN(C3C4C(=CC(=CC=4)Cl)N=CC=3)CC2)CC1.O
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| InChi Key |
AMCQDGFOKTXHSY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H32Cl2N6.4H3O4P.4H2O/c30-22-2-4-24-26(20-22)32-8-6-28(24)36-16-12-34(13-17-36)10-1-11-35-14-18-37(19-15-35)29-7-9-33-27-21-23(31)3-5-25(27)29;4*1-5(2,3)4;;;;/h2-9,20-21H,1,10-19H2;4*(H3,1,2,3,4);4*1H2
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| Chemical Name |
7-chloro-4-[4-[3-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]propyl]piperazin-1-yl]quinoline;phosphoric acid;tetrahydrate
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| Synonyms |
Piperaquine phosphate hydrate; Piperaquine phosphate; Piperaquine tetraphosphate hydrate
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~6 mg/mL (~6.00 mM)
DMSO : ~5 mg/mL (~5.00 mM) |
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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 | 1.0005 mL | 5.0023 mL | 10.0045 mL | |
| 5 mM | 0.2001 mL | 1.0005 mL | 2.0009 mL | |
| 10 mM | 0.1000 mL | 0.5002 mL | 1.0005 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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