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Purity: ≥98%
| Targets |
Elongation factor 2 (eEF2) and CaMKIII in Plasmodium falciparum. DDD107498 exerts its biological effects by inhibiting protein synthesis through targeting elongation factor 2 (eEF2), exhibiting an EC50 of 2 nM for wild-type Pf-eEF2. The compound also targets CaMKIII. Protein synthesis inhibition leads to parasite death and prevents the development of multiple life-cycle stages.
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| ln Vitro |
In tigers, carbaquine (24–48 hours) decreases protein synthesis, trophozoite and schizont development, and produces abnormalities in culture [1]. With EC50 = 1.0 nM, EC90 = 2.4 nM, and EC99 = 5.9 nM against the 3D7 tiger, carbaquine has outstanding activity[1]. In conjunction with hepatocytes or liver microsomes, camequinine has good metabolic stability [1].
DDD107498 demonstrates potent activity against multiple life-cycle stages of the Plasmodium falciparum parasite, with an EC50 of 1 nM for the 3D7 strain. The compound inhibits protein synthesis through targeting of elongation factor 2 (eEF2) and CaMKIII, exhibiting an EC50 of 2 nM for wild-type Pf-eEF2. It shows activity against both asexual blood stages and gametocytes. |
| ln Vivo |
In guinea pigs infected with odontozoan monkeys, carbaquine (oral, single dose) showed an ED90 (90% reduction in parasites) of 0.57 mg/kg [1]. Oral carbaquine at a dose of 3 mg/kg showed an 80 ng/mL Cmax, a 4-hour Tmax, an AUC of 200542 ng·min/mL, and a F (%) of 84% [2].
DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking, and chemoprotection. In vivo efficacy studies in mouse models of malaria have shown that DDD107498 can clear parasitemia and provide protection against infection. The compound's activity against multiple life-cycle stages supports its potential for malaria elimination efforts. |
| Enzyme Assay |
In vitro enzyme inhibition assays for DDD107498 are performed using recombinant Pf-eEF2 enzyme. The assay measures protein synthesis activity using a cell-free translation system or by monitoring the incorporation of radiolabeled amino acids into protein. DDD107498 is incubated at varying concentrations, and the inhibition of protein synthesis is quantified. EC50 values are calculated from dose-response curves.
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| Cell Assay |
Cellular assays for DDD107498 are performed using P. falciparum cultures in vitro. Parasites are treated with DDD107498 at varying concentrations, and parasite growth is assessed by measuring incorporation of 3H-hypoxanthine or by fluorescence-based methods using SYBR Green or other DNA-binding dyes. The EC50 for the 3D7 strain is 1 nM. Activity against gametocytes and liver stages can also be assessed.
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| Animal Protocol |
In vivo animal studies for DDD107498 are typically performed in mouse models of malaria. Mice are infected with P. berghei or P. falciparum and then treated with DDD107498 via oral administration at various doses. Parasitemia is monitored by blood smears, and survival is recorded. The compound's potential for single-dose treatment, transmission blocking, and chemoprotection is evaluated.
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| ADME/Pharmacokinetics |
DDD107498 has a molecular weight of 462.56 and molecular formula C27H31FN4O2. It is soluble in DMSO (93 mg/mL) and water (93 mg/mL). The compound is typically supplied as a solid. For in vivo studies, oral formulations are used. The compound has favorable physicochemical properties for oral bioavailability. Standard storage conditions apply.
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| Toxicity/Toxicokinetics |
Toxicological data for DDD107498 are limited to preclinical studies. The compound has been evaluated in animal models for safety and tolerability. As an antimalarial candidate, comprehensive toxicology studies would be required before clinical development. Standard laboratory safety precautions should be followed when handling DDD107498.
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| References |
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| Additional Infomation |
DDD107498 (Cabamiquine, M5717) is a multiple-stage antimalarial agent that inhibits protein synthesis through targeting of elongation factor 2 (eEF2). It demonstrates potent activity against multiple life-cycle stages of Plasmodium falciparum with an EC50 of 1 nM for the 3D7 strain. The compound shows potential for single-dose treatment, transmission blocking, and chemoprotection. DDD107498 is a research compound and has been studied in preclinical and early clinical settings. It represents a promising candidate for malaria treatment and elimination efforts.
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| Molecular Formula |
C27H31FN4O2
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| Molecular Weight |
462.5694
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| Exact Mass |
462.243
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| CAS # |
1469439-69-7
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| Related CAS # |
Cabamiquine succinate;2444781-71-7
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| PubChem CID |
71748268
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| Appearance |
White to off-white solid powder
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| Density |
1.229±0.06
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| Boiling Point |
649.5±55.0 °C
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
647
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BENUHBSJOJMZEE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H31FN4O2/c28-22-7-8-25-23(17-22)24(27(33)29-9-12-31-10-1-2-11-31)18-26(30-25)21-5-3-20(4-6-21)19-32-13-15-34-16-14-32/h3-8,17-18H,1-2,9-16,19H2,(H,29,33)
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| Chemical Name |
6-fluoro-2-(4-(morpholinomethyl)phenyl)-N-(2-(pyrrolidin-1-yl)ethyl)quinoline-4-carboxamide
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| Synonyms |
DDD107498 DDD-107498 DDD 107498 DDD 498 DDD-498 DDD498 MMV121 MMV-121 MMV 121
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~216.19 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.40 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.40 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 25.0 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: ≥ 2.5 mg/mL (5.40 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 | 2.1618 mL | 10.8092 mL | 21.6183 mL | |
| 5 mM | 0.4324 mL | 2.1618 mL | 4.3237 mL | |
| 10 mM | 0.2162 mL | 1.0809 mL | 2.1618 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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