DNDI-VL-2098
DNDI-VL-2098 is an orally active antileishmanial agent. DNDI-VL-2098 exhibits high permeability, in vitro metabolic stability, and selective inhibition of CYP2C19 (IC50=0.47 μM). DNDI-VL-2098 does not affect the activities of other major CYP enzymes (CYP1A2, CYP2C9, CYP2D6 and CYP3A4) at concentrations up to 12.5 μM. It shows favorable pharmacokinetic properties in multiple animal models including mice, hamsters, rats and dogs. DNDI-VL-2098 is characterized by moderate to high plasma protein binding and can be used for the research of visceral leishmaniasis.
For research use only. We do not sell to patients.
- CAS No.: 681492-17-1
- Formula: C14H12F3N3O5
- Molecular Weight:359.26
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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Leishmania |
CYP2C19 0.47 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| J774.A1 | IC50 |
0.03 μM
Compound: 9
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Antileishmanial activity against amastigote stage of Leishmania donovani infected in mouse J-774A.1 cells assessed as parasite growth inhibition after 72 hrs by luciferase reporter gene assay
Antileishmanial activity against amastigote stage of Leishmania donovani infected in mouse J-774A.1 cells assessed as parasite growth inhibition after 72 hrs by luciferase reporter gene assay
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[PMID: 26901446] |
| MRC5 | IC50 |
>64 μM
Compound: 9
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Cytotoxicity against human MRC5 cells assessed as cell viability incubated for 72 hrs by fluorimetric assay
Cytotoxicity against human MRC5 cells assessed as cell viability incubated for 72 hrs by fluorimetric assay
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[PMID: 26901446] |
| MRC5 | IC50 |
2.6 μM
Compound: 9
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Antitrypanosomal activity against Trypanosoma cruzi infected in human MRC5 cells assessed as parasite growth inhibition incubated for 7 days by chlorophenol red alpha-D-galactopyranoside-based assay
Antitrypanosomal activity against Trypanosoma cruzi infected in human MRC5 cells assessed as parasite growth inhibition incubated for 7 days by chlorophenol red alpha-D-galactopyranoside-based assay
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[PMID: 26901446] |
DNDI-VL-2098 (0.3-30 μg/mL; 4 h) exhibits moderate to high plasma protein binding rates (94-98%) with free fractions of 3-6% in mouse, rat, dog and human samples[1].
DNDI-VL-2098 exhibits potent activity in the macrophage amastigote model, with an IC50 of 0.025 μM against antimony-resistant Leishmania donovani strain DD8 and an IC50 of 0.7-2.6 μM against African clinical isolates[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Macrophage amastigote model
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Concentration:IC50 assay
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Incubation Time:24-48 h
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Result:Against the antimony-resistant Leishmania donovani DD8 strain with an IC50 of 0.025 μM, and against African clinical strains with IC50 values of 0.7-2.6 μM.
| Species | Dose | Route | C0 | AUClast | CLblood | Vss | T1/2 | Tmax | Cmax | Bioavailability |
|---|---|---|---|---|---|---|---|---|---|---|
| Golden hamster[1] | 1 mg/kg | i.v. | 1.14 μg/mL | 0.63 μg·h/mL | 25.98 mL/min/kg | 2.00 L/kg | 1.19 h | / | / | / |
| Golden hamster[1] | 6.25 mg/kg | p.o. | / | 4.49 μg·h/mL | / | / | / | 0.25 h | 1.17 μg/mL | 115 % |
| Golden hamster[1] | 12.5 mg/kg | p.o. | / | 17.13 μg·h/mL | / | / | / | 0.50 h | 2.36 μg/mL | / |
| Golden hamster[1] | 25 mg/kg | p.o. | / | 29.80 μg·h/mL | / | / | / | 4.00 h | 3.13 μg/mL | / |
| Golden hamster[1] | 50 mg/kg | p.o. | / | 53.00 μg·h/mL | / | / | / | 4.00 h | 4.93 μg/mL | / |
| Mice[1] | 1 mg/kg | i.v. | 0.74 μg/mL | 1.65 μg·h/mL | 9.37 mL/min/kg | 1.98 L/kg | 2.94 h | / | / | / |
| Mice[1] | 6.25 mg/kg | p.o. | / | 13.10 μg·h/mL | / | / | / | 2.00 h | 1.08 μg/mL | 127 % |
| Mice[1] | 12.5 mg/kg | p.o. | / | 29.76 μg·h/mL | / | / | / | 4.00 h | 2.43 μg/mL | / |
| Mice[1] | 25 mg/kg | p.o. | / | 77.23 μg·h/mL | / | / | / | 4.00 h | 5.39 μg/mL | / |
| Mice[1] | 50 mg/kg | p.o. | / | 145.08 μg·h/mL | / | / | / | 6.00 h | 8.39 μg/mL | / |
| Rat[1] | 1 mg/kg | i.v. | 0.56 μg/mL | 1.84 μg·h/mL | 8.18 mL/min/kg | 2.24 L/kg | 3.44 h | / | / | / |
| Rat[1] | 5 mg/kg | p.o. | / | 10.96 μg·h/mL | / | / | / | 1.81 h | 0.86 μg/mL | 119 % |
| Rat[1] | 5 mg/kg | p.o. | / | 6.64 μg·h/mL | / | / | / | 4.50 h | 0.57 μg/mL | 72 % |
| Rat[1] | 50 mg/kg | p.o. | / | 76.22 μg·h/mL | / | / | / | 5.00 h | 7.13 μg/mL | / |
| Rat[1] | 100 mg/kg | p.o. | / | 187.14 μg·h/mL | / | / | / | 6.50 h | 9.99 μg/mL | / |
| Rat[1] | 200 mg/kg | p.o. | / | 351.77 μg·h/mL | / | / | / | 7.50 h | 12.75 μg/mL | / |
DNDI-VL-2098 (25 mg/kg) achieves a parasite inhibition rate of over 85% in a hamster model of chronic visceral leishmaniasis, with higher efficacy than its racemate and (S)-enantiomer[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Swiss Albino mice with Visceral Leishmaniasis[1]
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Dosage:50 mg/kg
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Administration:once daily; 5 days; p.o.
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Result:Achieved greater than 99% parasite inhibition.
Chemical Information
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CAS No. 681492-17-1
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Molecular Weight 359.26
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Formula C14H12F3N3O5
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SMILES
FC(F)(F)OC(C=C1)=CC=C1OC[C@@]2(OC3=NC([N+]([O-])=O)=CN3C2)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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