| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
Cipargamin targets the Plasmodium falciparum ATP4 (PfATP4) ion pump, a P-type ATPase that plays a critical role in maintaining sodium ion homeostasis in the parasite. Inhibition of PfATP4 disrupts the parasite's intracellular sodium concentration, leading to metabolic derangement and ultimately parasite death. This mechanism is distinct from other antimalarial agents, making cipargamin effective against parasites resistant to artemisinin and other standard therapies. The compound also inhibits gametocytogenesis and blocks transmission to the mosquito vector.
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| ln Vitro |
At the highest studied concentration (10 μM), cipragamin (NITD609) is non-toxic to human foreskin fibroblasts (HFF) and inhibits Toxoplasma gondii, with a tachyzoite MIC90 of 5 μM and a MIC50 of 1 μM [1]. At 50 and 500 nM, the most effective inhibitor of early gametocyte growth is ciprgamin (NITD609). The formation of late gametocytes is inhibited by sipragamine in a dose-dependent manner [2]. With ICIC50 values ranging from 0.5 to 1.4 nM, cipragmin (NITD609) demonstrates strong efficacy against a panel of Plasmodium falciparum strains that have been culture-adapted. Like artesunate, sipargamine is active against all isolates of P. falciparum and P. vivax in the low nanomolar range (ICIC50 values consistently <10 nM) [3].
Cipargamin exhibits potent in vitro activity against Plasmodium falciparum with an IC50 of approximately 1 nM. It also inhibits Toxoplasma gondii with a MIC50 of 1 μM and a MIC90 of 5 μM for tachyzoites. At concentrations up to 10 μM, cipargamin is non-toxic to human foreskin fibroblasts (HFF), indicating a favorable selectivity index. The compound's potency against multidrug-resistant strains and its activity against both asexual blood stages and gametocytes highlight its potential as a next-generation antimalarial. |
| ln Vivo |
In malaria mouse models, dipergamin (NITD609) has good pharmacokinetic features and single-dose curative effectiveness. In all treated mice, cipramer (100 mg/kg) totally eradicated Plasmodium berghei infection; a single oral dose of 30 mg/kg produced a 50% partial cure [3].
Cipargamin demonstrates rapid parasite clearance in vivo and is effective against blood-stage parasites. It has shown promising results in preclinical studies and is currently in clinical trials for the treatment of malaria. The compound's favorable pharmacokinetics and oral bioavailability make it a promising candidate for malaria treatment. In animal models, cipargamin has demonstrated efficacy against Plasmodium infections, including those caused by drug-resistant strains. Its ability to block transmission to mosquitoes further supports its potential in malaria elimination efforts. |
| Enzyme Assay |
In vitro enzyme assays for cipargamin involve measuring the inhibition of PfATP4-associated Na+-ATPase activity. Parasite lysates or recombinant PfATP4 are incubated with ATP and sodium ions in the presence of varying concentrations of cipargamin. The release of inorganic phosphate is measured colorimetrically to determine ATPase activity. IC50 values are calculated from dose-response curves. Additional assays may assess the compound's effect on parasite intracellular sodium levels using fluorescent sodium indicators or atomic absorption spectroscopy.
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| Cell Assay |
Cellular assays for cipargamin are performed using cultured P. falciparum parasites (e.g., 3D7 or Dd2 strains) in human red blood cells. Parasites are cultured in RPMI medium supplemented with human serum and treated with serial dilutions of cipargamin for 48-72 hours. Parasite growth is assessed by measuring [3H]-hypoxanthine incorporation or by fluorescence-based methods using SYBR Green I. IC50 values are determined from dose-response curves. Cytotoxicity is assessed in human cell lines (e.g., HepG2 or HFF) using standard MTT assays.
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| Animal Protocol |
In vivo efficacy studies for cipargamin are conducted in mouse models of malaria (e.g., P. berghei or P. falciparum-infected SCID mice). Infected mice are treated with cipargamin orally or intravenously at various doses (typically 1-30 mg/kg) for 4 days. Parasitemia is monitored by Giemsa-stained blood smears or flow cytometry. The compound's ability to cure infection and prevent recrudescence is assessed. Transmission-blocking activity is evaluated using standard membrane feeding assays with Anopheles mosquitoes.
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| ADME/Pharmacokinetics |
Cipargamin demonstrates favorable pharmacokinetic properties, including good oral bioavailability and rapid absorption. In preclinical studies, it shows a half-life compatible with once-daily dosing. The compound is metabolized primarily in the liver, with metabolites excreted in urine and feces. Its distribution to tissues is adequate for antimalarial activity, with good penetration into red blood cells where the parasite resides. The favorable PK profile supports its clinical development as a potential single-dose or short-course treatment for malaria.
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| Toxicity/Toxicokinetics |
Cipargamin has been shown to be non-toxic to human foreskin fibroblasts at concentrations up to 10 μM. In preclinical toxicology studies, the compound has demonstrated a favorable safety profile with no significant adverse effects at therapeutic doses. However, comprehensive toxicological data from clinical trials are still being evaluated. The compound's selectivity for parasite PfATP4 over human ATPases contributes to its low toxicity. Ongoing clinical trials are assessing its safety and tolerability in humans.
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| References |
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| Additional Infomation |
Cipargamin has been used in trials studying malaria treatment, cure rates, and Plasmodium falciparum malaria.
Cipargamin (NITD609/KAE609) is a spiroindolone antimalarial discovered through a phenotypic screening campaign. It is currently in clinical development for the treatment of uncomplicated malaria. The compound's novel mechanism of action—inhibition of PfATP4—makes it a promising candidate for combating drug-resistant malaria. It also shows transmission-blocking activity, supporting its potential use in malaria elimination programs. Cipargamin is not yet approved for clinical use but represents a significant advancement in antimalarial drug development. |
| Molecular Formula |
C19H14CL2FN3O
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|---|---|
| Molecular Weight |
390.2394
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| Exact Mass |
389.049
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| CAS # |
1193314-23-6
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| PubChem CID |
44469321
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| Appearance |
Light brown to brown solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
621.3±55.0 °C at 760 mmHg
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| Flash Point |
329.6±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.738
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| LogP |
4.61
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
26
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| Complexity |
609
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H]1CC2=C([C@]3(N1)C4=C(C=CC(=C4)Cl)NC3=O)NC5=CC(=C(C=C25)F)Cl
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| InChi Key |
CKLPLPZSUQEDRT-WPCRTTGESA-N
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| InChi Code |
InChI=1S/C19H14Cl2FN3O/c1-8-4-11-10-6-14(22)13(21)7-16(10)23-17(11)19(25-8)12-5-9(20)2-3-15(12)24-18(19)26/h2-3,5-8,23,25H,4H2,1H3,(H,24,26)/t8-,19+/m0/s1
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| Chemical Name |
(3R,3'S)-5,7'-dichloro-6'-fluoro-3'-methylspiro[1H-indole-3,1'-2,3,4,9-tetrahydropyrido[3,4-b]indole]-2-one
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| Synonyms |
GNF609 KAE609, KAE 609,GNF 609 NITD609, NITD 609, NITD-609, KAE-609, GNF-609
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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) |
DMSO : ~50 mg/mL (~128.13 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (7.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5625 mL | 12.8126 mL | 25.6253 mL | |
| 5 mM | 0.5125 mL | 2.5625 mL | 5.1251 mL | |
| 10 mM | 0.2563 mL | 1.2813 mL | 2.5625 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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