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1mg |
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10mg |
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25mg |
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Purity: ≥98%
APX001A (Manogepix, E1210) is a first-in-class, broad-spectrum and orally bioactive inhibitor of the fungal protein Gwt1 (GPI-anchored wall transfer protein 1) in the glycosylphosphatidylinositol (GPI) biosynthesis pathway. Gwt1 protein is an enzyme required for acylation of inositol during glycosylphosphatidylinositol anchor biosynthesis. Manogepix (APX001A) is the active metabolite of fosmanogepix (APX001), which is a drug candidate currently in clinical trials for the treatment of invasive fungal infections. APX001A is active against the major fungal pathogens, i.e., Candida (except Candida krusei), Aspergillus, and hard-to-treat molds, including Fusarium and Scedosporium.
ln Vitro |
Manogepix has no inhibitory effect against human Pig-Wp even at concentrations as high as 100 μM, but it does reduce the inositol acylation activity of C. albicans Gwt1p and A. fumigatus Gwt1p with IC50s of 0.3 to 0.6 μM. The expression of GPI-anchored protein ALS1 on the surfaces of Candida albicans cells treated with Manogepix is examined and shown to be much lower than that on untreated cells, confirming the inhibition of fungal glycosylphosphatidylinositol (GPI) biosynthesis. At concentrations above its minimum inhibitory concentration (MIC), manogepix inhibits the production of germ tubes, adhesion to polystyrene surfaces, and biofilm formation of Candida albicans [1].
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ln Vivo |
The quantity of viable C is decreased by manogepix treatment (oral administration; twice daily; for three days; specific-pathogen-free female ICR mice; 2.5 mg/kg, 5 mg/kg, and 10 mg/kg). oral cavity albicans cells in a dose-dependent way[2].
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Animal Protocol |
Animal/Disease Models: Specific-pathogen-free female ICR mice (5 weeks; ~25 g) with C. albicans[2]
Doses: 2.5 mg/kg, 5 mg/kg and 10 mg /kg Route of Administration: Oral administration; twice (two times) daily; for 3 days Experimental Results: decreased the number of viable C. albicans cells in the oral cavity in a dose-dependent manner. |
References |
[1]. Watanabe NA, et al. E1210, a new broad-spectrum antifungal, suppresses Candida albicans hyphal growth through inhibition of glycosylphosphatidylinositol biosynthesis. Antimicrob Agents Chemother. 2012 Feb;56(2):960-71.
[2]. Hata K, et al. Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis. Antimicrob Agents Chemother. 2011 Oct;55(10):4543-51. |
Molecular Formula |
C21H18N4O2
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Molecular Weight |
358.4
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Exact Mass |
358.143
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CAS # |
936339-60-5
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Related CAS # |
Fosmanogepix;2091769-17-2
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SMILES |
NC1=NC=CC=C1C2=CC(CC3=CC=C(COC4=NC=CC=C4)C=C3)=NO2
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Chemical Name |
(3-(3-(4-(((Pyridin-2-yl)oxy)methyl)benzyl)isoxazol-5-yl)pyridin-2-)amine
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Synonyms |
E1210 APX001AE-1210 APX 001 AE 1210 APX-001-AAPX001-A Manogepix
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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 (~279.03 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.80 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 (5.80 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 (5.80 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 | 2.7902 mL | 13.9509 mL | 27.9018 mL | |
5 mM | 0.5580 mL | 2.7902 mL | 5.5804 mL | |
10 mM | 0.2790 mL | 1.3951 mL | 2.7902 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.