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GNF179 is an optimized 8,8-dimethyl IP analog that exhibited the potency(4.8 nM against the multidrug resistant strain W2) in vitro metabolic stability and in vivo oral bioavailability. IC50 value: 4.8 nM. Target: Anti-parasitic agent GNF179 exhibits a low clearance (CL=22 ml/min/kg, ~25% of hepatic blood flow in mice), a large volume of distribution (steady-state volume of distribution, Vss=11.8 l/kg), a moderate residence time (MRT=9 hours) and suitable terminal half-life (t1/2=8.9 hours). GNF179 reduced Plasmodium berghei parasitemia levels by 99.7% with a single 100 mg/kg oral dose, and prolonged mouse survival by an average of 19 days. GNF179 was able to protect against an infectious P. berghei sporozoite challenge with a single oral dose at 15 mg/kg while NITD609 was not.
| Cell Experiment | |
|---|---|
| Cell lines | P. falciparum Asexual Blood Stage |
| Preparation method | The half maximal inhibitory concentration (IC50) of GNF179 was determined to be 9.0 nM using a 72 hr SYBR® Green I drug sensitivity assay. |
| Concentrations | 40 nM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 427.9 |
| Formula | C22H23ClFN5O |
| CAS Number | 1261114-01-5 |
| Form | Solid |
| Solubility (25°C) | 10 mM in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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