APX2039
Based on 1 Customer Validation
APX2039 is a brain-penetrant and orally active Gwt1 protein inhibitor. APX2039 inhibits an early step in fungal glycosylphosphatidylinositol anchor biosynthesis. APX2039 can be used for the research of cryptococcal meningitis and invasive mycosis caused by Talaromyces marneffei.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 98.44%
- No. CAS: 2342606-49-7
- Fòrmula: C20H15FN4O2
- Peso molecular:362.36
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
Descripciòn
In Vitro
APX2039 (0.008 μg/mL) potently inhibits Cryptococcus neoformans var. grubii H99 in vitro with an MIC of 0.008 μg/mL[1].
APX2039 (0.008-4 µg/mL; 72 h) inhibits growth of clinical Talaromyces marneffei isolates in vitro with a geometric mean MIC of 0.98 µg/mL, an MIC50 of 1 µg/mL, and an MIC90 of 5 µg/mL, with individual MIC values ranging from 0.25 µg/mL to 4 µg/mL[2].
APX2039 (0.002-2 μg/mL; 40-72 h) potently inhibits the growth of Cryptococcus neoformans H99 (MIC = 0.008 μg/mL), Cryptococcus gattii WM276 (MIC = 0.004 μg/mL), Candida albicans 90028 (MIC = 0.031 μg/mL), and Aspergillus fumigatus MYA3626 (MEC = 0.125 μg/mL) in vitro[3].
APX2039 (0.002-2 μg/mL; 72 h) potently inhibits the growth of 18 clinical Cryptococcus neoformans and Cryptococcus gattii isolates (including Fluconazole (HY-B0101)-resistant strains) in vitro, with an MIC range of 0.004 to 0.031 μg/mL and an MIC90 of 0.031 μg/mL[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
APX2039 (25-75 mg/kg; p.o.; QD/BID; 13 days) plus ABT at 50 mg/kg p.o. BID achieves a rapid, undetectable CSF fungal burden by day 10 and a 6.6 log10 CFU/g reduction in brain fungal burden in a rabbit model of Cryptococcus meningitis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD-1 (male, 22 to 24 g, infected via tail vein injection with Cryptococcus neoformans strain H99)[1]
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Dosage:60 mg/kg plus 50 mg/kg ABT
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Administration:p.o.; QD; 7 days
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Result:Reduced mean lung fungal burden by 4.45 log10 CFU/g (from control mean of 5.95 log10 CFU/g to 1.50 log10 CFU/g).
Reduced mean brain fungal burden by 6.53 log10 CFU/g (from control mean of 7.97 log10 CFU/g to 1.44 log10 CFU/g).
Achieved fungal burden below the limit of detection.
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Animal Model:New Zealand White (male, 2.3 to 3.1 kg, immunosuppressed with daily hydrocortisone acetate, inoculated via cisterna magna injection with Cryptococcus neoformans strain H99)[1]
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Dosage:25 mg/kg; 50 mg/kg; 75 mg/kg
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Administration:p.o.; QD/BID; 13 days
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Result:Reduced CSF fungal burden from an average baseline of 4.75 log10 CFU/mL to undetectable levels by day 10 postinfection at 50 mg/kg BID, with a total mean reduction of 4.6 log10 CFU/mL over 8 days of treatment.
Exhibited effective fungicidal activity ranging from -0.53 to -0.66 log10 CFU/mL/day at 50 mg/kg BID.
Reduced brain tissue fungal burden by a mean of 6.6 log10 CFU/g at 50 mg/kg BID, with undetectable levels in cerebellum/brainstem and cerebrum, and demonstrated significantly superior efficacy to fluconazole and amphotericin B (adjusted P = 0.027 for both).
Achieved mean total CSF fungal burden reduction of 2.7 log10 CFU/mL by day 14 at 75 mg/kg QD, with a fungal clearance rate of -0.34 log10 CFU/mL/day.
Achieved mean total CSF fungal burden reduction of 0.72 log10 CFU/mL by day 14 at 50 mg/kg QD, with a fungal clearance rate of -0.06 log10 CFU/mL/day.
Showed no effective reduction at 25 mg/kg QD, with a small mean increase of 0.07 log10 CFU/mL by day 14, equivalent to vehicle control.
Achieved near-maximal antifungal activity with a total drug AUC0-24 of 25 to 50 mg·h/L.
Chemical Information
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No. CAS 2342606-49-7
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Appearance Solid
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Peso molecular 362.36
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Fòrmula C20H15FN4O2
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Color Off-white to light yellow
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SMILES
NC1=NC=CC=C1C2=CC(CC3=CC=C(C=C3)OC4=NC(F)=CC=C4)=NO2
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (275.97 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureza y Documentación
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Ficha de datos (281 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Giamberardino CD, et al. Efficacy of APX2039 in a Rabbit Model of Cryptococcal Meningitis. mBio. 2022;13(6):e0234722. [Content Brief]
[3]. Shaw KJ, et al. In Vitro and In Vivo Evaluation of APX001A/APX001 and Other Gwt1 Inhibitors against Cryptococcus. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00523-18. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7597 mL | 13.7984 mL | 27.5969 mL | 68.9922 mL |
| 5 mM | 0.5519 mL | 2.7597 mL | 5.5194 mL | 13.7984 mL | |
| 10 mM | 0.2760 mL | 1.3798 mL | 2.7597 mL | 6.8992 mL | |
| 15 mM | 0.1840 mL | 0.9199 mL | 1.8398 mL | 4.5995 mL | |
| 20 mM | 0.1380 mL | 0.6899 mL | 1.3798 mL | 3.4496 mL | |
| 25 mM | 0.1104 mL | 0.5519 mL | 1.1039 mL | 2.7597 mL | |
| 30 mM | 0.0920 mL | 0.4599 mL | 0.9199 mL | 2.2997 mL | |
| 40 mM | 0.0690 mL | 0.3450 mL | 0.6899 mL | 1.7248 mL | |
| 50 mM | 0.0552 mL | 0.2760 mL | 0.5519 mL | 1.3798 mL | |
| 60 mM | 0.0460 mL | 0.2300 mL | 0.4599 mL | 1.1499 mL | |
| 80 mM | 0.0345 mL | 0.1725 mL | 0.3450 mL | 0.8624 mL | |
| 100 mM | 0.0276 mL | 0.1380 mL | 0.2760 mL | 0.6899 mL |
APX2039 Related Classifications
HY-147110 Related Classifications
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Keywords
- APX2039
- 2342606-49-7
- APX 2039
- APX-2039
- Fungal
- cryptococcal meningitis
- Aspergillus fumigatus MYA3626
- invasive mycosis
- Cryptococcus neoformans var. grubii H99
- Talaromyces marneffei
- glycosylphosphatidylinositol anchor biosynthesis
- blood-brain barrier
- Cryptococcus gattii WM276
- Gwt1 protein
- Candida albicans 90028
- Inhibitor
- inhibitor
- inhibit