| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
GNF179, an optimized 8,8-dimethyl imidazolopiperazine analog, is a novel, potent and orally bioavailable antiparasitic agent that exhibited the potency(4.8 nM against the multidrug resistant strain W2) in vitro metabolic stability and in vivo oral bioavailability. Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable.
| ln Vitro |
Atovaquone's liver-stage target, plasmid cytochrome bc1, is unlikely to be induced by GNF179 and does not quickly block plasmid protein production. GNF179 (5-100 nM; 48 h) eliminates oocyst production at 5 nM and is very suppressive to sexual life cycle advancement in princely gametocytes [2]. It is possible that GNF179 acts on sporophytes rather than the liver stage [1].
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| ln Vivo |
Rodent malaria models demonstrate the antimalarial activity of GNF179 (15 mg/kg; po; single dose) [1].
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| Animal Protocol |
Animal/Disease Models: Naïve balb/c (Bagg ALBino) mouse infected with P. berghei[1]
Doses: 15 mg/kg Route of Administration: po (po (oral gavage)) single dose Experimental Results:Protected against an infectious P. berghei sporozoite. Animal/Disease Models: First exposure to balb/c (Bagg ALBino) mouse[ 1] Doses: 3 or 20 mg/kg Route of Administration: IV or PO (pharmacokinetic/PK/PK analysis) Experimental Results: pharmacokinetic/PK/PKs of GNF179 in naïve balb/c (Bagg ALBino) mouse. Dose AUC(0-∞) (hrs*µM) AUC/dose t1/2 (hrs) MRT (hrs) CL (ml/min/kg) Vss (L/kg) C0 or Cmax (µM) F (%) 3 mg/kg iv 8.88 3.0 8.9 9.0 22 11.8 6.1 nd 20 mg/kg po 20.70 1.0 8.4 nd nd 1.2 58 AUC, area under the curve; T1/2, half-life; CL, clearance; VSS, steady-state volume of distribution; C0, initial Concentration; Cmax maximum concentration; F, fraction of absorbed dose; hrs (hrs (hours)), hrs (hrs (hours)); nd, not determined. |
| References |
|
| Molecular Formula |
C22H23CLFN5O
|
|---|---|
| Molecular Weight |
427.9023
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| Exact Mass |
427.158
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| CAS # |
1261114-01-5
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| Related CAS # |
GNF179 (Metabolite);1310455-86-7
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| PubChem CID |
58178960
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.833
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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
|
| Heavy Atom Count |
30
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| Complexity |
606
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| Defined Atom Stereocenter Count |
0
|
| InChi Key |
KFSKTWYDIHJITF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H23ClFN5O/c1-22(2)21-27-19(14-3-7-16(24)8-4-14)20(26-17-9-5-15(23)6-10-17)28(21)11-12-29(22)18(30)13-25/h3-10,26H,11-13,25H2,1-2H3
|
| Chemical Name |
2-amino-1-(3-((4-chlorophenyl)amino)-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)ethanone
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| Synonyms |
GNF179; GNF-179; GNF 179
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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 : ~100 mg/mL (~233.70 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.86 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 20.8 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: ≥ 2.08 mg/mL (4.86 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 20.8 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: ≥ 2.08 mg/mL (4.86 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 | 2.3370 mL | 11.6850 mL | 23.3699 mL | |
| 5 mM | 0.4674 mL | 2.3370 mL | 4.6740 mL | |
| 10 mM | 0.2337 mL | 1.1685 mL | 2.3370 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.
 Images of high-content screening of parasite hepatic schizonts and parasite growth dynamics. |
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The effect of GNF179 on the liver stage parasite and a comparison with lasalocid, pyrimethamine and atovaquone. |
SNPs identified inpfcarlby microarray analysis and whole genome sequencing analysis. |
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