| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
The primary target of Arterolane is the parasite's hemoglobin digestion process. Ozonides are activated by heme iron in the parasite's digestive vacuole, leading to the generation of reactive carbon radicals that alkylate essential parasite proteins. This results in rapid parasite killing. Arterolane has a unique mechanism that is distinct from artemisinin derivatives, potentially overcoming resistance to artemisinin-based therapies.
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| ln Vitro |
Arterolane (Trioxolane 7; OZ277; RBx-11160) is an antimalarial medication with IC50 values of 1.1 nM (0.43 ng/mL) for P. falciparum Ro73 and W2, respectively. Arterolane also inhibited several other Plasmodium falciparum species, with IC50 values of 1.0, 1.6, 0.90, 0.91, 1.4, 1.5, 0.83, and 0.84 ng/mL for P. falciparum K1, Fc27, FVO, NF54, HB3, and FCB1. They are ITG2-F6 and MAD20[1], respectively.
In vitro, Arterolane demonstrates potent antiplasmodial activity with IC₅₀ values in the single-digit nanomolar range against both chloroquine-sensitive and -resistant strains. It is active against all asexual blood stages of the parasite. In drug combination studies, it shows synergistic effects with other antimalarials like piperaquine. Its activity is measured using standard parasite growth inhibition assays with [³H]hypoxanthine incorporation. |
| ln Vivo |
In vivo, Arterolane has shown excellent efficacy in mouse models of malaria. Oral administration at low doses completely clears parasitemia in P. berghei-infected mice. It also has a long duration of action, with single doses providing cure in some models. In human clinical trials, it has demonstrated efficacy and safety, and it is often combined with piperaquine to prevent resistance.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Arterolane are not typical, as it acts via a non-specific chemical mechanism. However, its activation by heme can be studied in vitro by measuring the production of reactive intermediates using spin trapping or mass spectrometry. The compound's stability in the presence of heme can be assessed.
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| Cell Assay |
In vitro cell-based assays for Arterolane involve culturing P. falciparum in red blood cells and measuring parasite growth inhibition. Serial dilutions of the compound are added to synchronized parasite cultures, and after incubation, [³H]hypoxanthine incorporation is measured to determine IC₅₀ values. Cytotoxicity against mammalian cell lines (e.g., HepG2, HEK293) is assessed to evaluate selectivity.
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| Animal Protocol |
In vivo animal studies for Arterolane utilize mouse models of malaria. Mice are infected with P. berghei or P. yoelii, and the compound is administered orally at various doses. Parasitemia is monitored by blood smears, and survival is recorded. The compound's efficacy is compared to standard treatments like artemether-lumefantrine. Pharmacokinetic studies are often conducted concurrently.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Arterolane are characterized by excellent oral bioavailability and a long half-life (approximately 20-30 hours in humans). It is metabolized primarily by CYP3A4. The compound is highly protein-bound. Its long half-life allows for single-dose or once-daily dosing regimens. Storage is at -20°C.
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| Toxicity/Toxicokinetics |
The toxicity profile of Arterolane is generally favorable in preclinical studies, with no significant adverse effects at therapeutic doses. It does not show neurotoxicity or cardiotoxicity. However, as with all antimalarials, mild gastrointestinal side effects have been reported. The compound is for research use and is being evaluated in clinical trials.
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| References | |
| Additional Infomation |
Arterolane is an oxaspirocyclic compound with the structure dispiro[cyclohexane-1,3'-[1,2,4]trioxacyclopentane-5',2''-tricyclo[3.3.1.1(3,7)]decane], substituted at the 4S position with 2-[(2-amino-2-methylpropyl)amino]-2-oxoethyl. Its maleate salt, in combination with piperaquine, is used as an antimalarial drug. It exhibits dual antimalarial and anti-malarial parasite activity. Arterolane belongs to the adamantane class, secondary amide class, primary amine class, trioxacyclopentane class, and oxaspirocyclic class. It is the conjugate base of Arterolane(1+).
Additional information: Arterolane is also known as OZ439 and artefenomel. It is a synthetic ozonide developed by the Medicines for Malaria Venture (MMV). It has completed Phase IIb clinical trials. This product is for research use only and is not approved for clinical or therapeutic applications. |
| Molecular Formula |
C22H36N2O4
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|---|---|
| Molecular Weight |
392.54
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| Exact Mass |
392.268
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| CAS # |
664338-39-0
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| Related CAS # |
664338-39-0
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| PubChem CID |
10475633
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| Appearance |
White to off-white solid powder
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| Density |
1.202 g/cm3
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| Boiling Point |
572.161ºC at 760 mmHg
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| Flash Point |
299.832ºC
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| LogP |
4.787
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
598
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VXYZBLXGCYNIHP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H36N2O4/c1-20(2,23)13-24-19(25)12-14-3-5-21(6-4-14)26-22(28-27-21)17-8-15-7-16(10-17)11-18(22)9-15/h14-18H,3-13,23H2,1-2H3,(H,24,25)
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| Chemical Name |
N-(2-Amino-2-methylpropyl)-2-{dispiro[adamantane-2,2'-[1,3,5]trioxolane-4',1''-cyclohexane]-4''-yl}acetamide
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| Synonyms |
RBx 11160RBx11160 RBx-11160 ArterolaneOZ 277OZ-277 OZ277
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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) |
DMSO : ~100 mg/mL (~254.76 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 16.7 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. Solubility in Formulation 2: ≥ 1.67 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.67 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5475 mL | 12.7376 mL | 25.4751 mL | |
| 5 mM | 0.5095 mL | 2.5475 mL | 5.0950 mL | |
| 10 mM | 0.2548 mL | 1.2738 mL | 2.5475 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03452475 | Completed | Drug: Arterolane-piperaquine Drug: Arterolane-piperaquine+mefloquine |
Plasmodium Falciparum | University of Oxford | March 7, 2018 | Phase 3 |
| NCT02461186 | Withdrawn | Drug: Arterolane maleate-piperaquine phosphate (Synriam) |
Uncomplicated Falciparum Malaria Artemisinin-resistant |
University of Oxford | June 2015 | Phase 2 Phase 3 |
| NCT00362050 | Completed | Drug: Treatment with 3 dose groups of RBx11160 over 7 days |
Plasmodium Falciparum Malaria | Medicines for Malaria Venture | June 2006 | Phase 2 |
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