Posaconazole (SCH 56592)

Alias: Posaconazole; Noxafil; SCH-56592; Schering 56592; Sch 56592; Schering 56592;
Cat No.:V1855 Purity: ≥98%
Posaconazole (also known as SCH 56592 or trade name of Noxafil) is a potent,broad-spectrum, second generation triazole antifungal compound that potently inhibits 14α-demethylation in a variety of fungi, including Candida and Aspergillus, with half maximal inhibition concentration IC50 of 0.007 μg/ml, 0.06 μg/ml, 0.2 μg/ml, 0.3 μg/ml, 0.03 μg/ml and 0.03 μg/ml respectively Posaconzole, an itraconzole derivative with fluorine replacing chlorine in the phenyl ring and hydroxylation in the side chain, binds to the heme cofactor on the active site of 14α-demethylase, which converts lanosterol to 14α-dimethy lanosterol, resulting in the disruption of the integrity and function of the fungal cell membrane and inhibition of fungal growth.
Posaconazole (SCH 56592) Chemical Structure CAS No.: 171228-49-2
Product category: Fungal
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
100mg
250mg
500mg
Other Sizes

Other Forms of Posaconazole (SCH 56592):

  • Posaconazole-D5
  • Posaconazole-D4
  • Posaconazole hydrate
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Posaconazole (also known as SCH 56592 or trade name of Noxafil) is a potent, broad-spectrum, second generation triazole antifungal compound that potently inhibits 14α-demethylation in a variety of fungi, including Candida and Aspergillus, with half maximal inhibition concentration IC50 of 0.007 μg/ml, 0.06 μg/ml, 0.2 μg/ml, 0.3 μg/ml, 0.03 μg/ml and 0.03 μg/ml respectively Posaconzole, an itraconzole derivative with fluorine replacing chlorine in the phenyl ring and hydroxylation in the side chain, binds to the heme cofactor on the active site of 14α-demethylase, which converts lanosterol to 14α-dimethy lanosterol, resulting in the disruption of the integrity and function of the fungal cell membrane and inhibition of fungal growth.

Biological Activity I Assay Protocols (From Reference)
ln Vitro

In vitro activity: Posaconazole has potent trypanocidal activity. Amiodarone acts synergistically with Posaconazole. Posaconazole also affects and disrupts Ca2+ homeostasis in T. cruzi. Posaconazole blocks the biosynthesis of ergosterol, which is essential for parasite survival. Posaconazole has a clear, dose-dependent effect on proliferation of the epimastigote (extracellular) stages, with a minimal inhibitory concentration of 20 nM and an IC50 of 14 nM. Against the clinically relevant intracellular amastigote form of the parasite, Posaconazole is even more potent. Posaconazole has the minimal inhibitory concentration and IC50 values of 3 nM and 0.25 nM. Posaconazole is active against isolates of Candida and Aspergillus spp. that exhibit resistance to Fluconazole, Voriconazole, and Amphotericin B and is much more active than the other triazoles against zygomycetes.


Cell Assay: The epimastigote form of the parasite is cultivated in liver infusion tryptose medium, supplemented with 10% new born calf serum at 28 °C with strong (120 rpm) agitation. Cultures are initiated at a cell density of 2 × 106 epimastigotes/mL, and Posaconazole is added at a cell density of 0.5−1.0 × 107 epimastigotes/mL. Cell densities are measured by using an electronic particle counter as well as by direct counting with a hemocytometer. Cell viability is followed by Trypan blue exclusion, using light microscopy. Amastigotes are cultured in Vero cells maintained in minimal essential medium supplemented with 1% fetal calf serum in a humidified atmosphere (95% air−5% CO2) at 37 °C. Cells are infected with 10 tissue culture-derived trypomastigotes per cell for 2 hours and then washed three times with phosphate-buffered saline (PBS) to remove nonadherent parasites. Fresh medium with and without Posaconazole is added, and the cells are incubated for 96 hours with a medium change at 48 hours. The percent of infected cells and the numbers of parasites per cell are determined directly using light microscopy, and a statistical analysis of the results is carried out. IC50 values are calculated by nonlinear regression, using the program GraFit. Fractional inhibitory concentrations (FIC) are calculated. Cytoplasmic free Ca2+ concentrations in control and drug-treated extracellular epimastigotes are determined by fluorimetric methods using Fura-2. Subcellular Ca2+ levels and mitochondrial membrane potentials are monitored on individual Vero cells infected with T. cruzi amastigotes by using time-scan confocal microscopy. Briefly, Vero cells heavily infected (72 hours) with T. cruzi amastigotes are plated onto 22 × 40 mm glass coverslips (0.15 mm thickness) and incubated simultaneously with 10 μM cell-permeant Rhod-2 and 10 μg/mL Rhodamine-123 for 50 minutes at 37 °C in culture medium and then washed and incubated with Ringers solution, with or without amiodarone. Under the conditions used fluorescence of Rhod-2 comes mainly from intracellular Ca2+-rich compartments, like mitochondria, since its low affinity for Ca2+ limits its fluorescence in the Ca2+-poor cytoplasm of the Vero cells or amastigotes. Rhodamine-123 is a mitochondrion-specific cationic dye, which distributes across the inner mitochondrial membranes strictly according to their membrane potential.

ln vivo
Treatment of infected animals with amiodarone alone reduces parasitemia, increases survival 60 days pi (0% for untreated controls vs 40% for amiodarone-treated animals) and, when given in combination with Posaconazole, delays the development of parasitemia. Coadministration of Posaconazole and Boost Plus increases drug exposure compared to the administration of Posaconazole alone in the fasted state. Food, particularly meals high in fat content, significantly increases Posaconazole bioavailability. Systemic exposure to Posaconazole increases 4- and 2.6-fold when it is consumed with a high-fat and nonfat meal, respectively. Posaconazole and Amiodarone may constitute an effective anti-T. cruzi therapy with low side effect. At twice-daily doses of ≥15 mg/kg of body weight, Posaconazole prolongs the survival of the mice and reduces tissue burden.
Animal Protocol
20 mg/kg/d; Oral gavage
Female NMRI IVIC mice with acute Chagas
References
J Med Chem.2006 Feb 9;49(3):892-9;Antimicrob Agents Chemother.2006 Jun;50(6):2009-15.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C37H42F2N8O4
Molecular Weight
700.78
Exact Mass
700.33
Elemental Analysis
C, 63.41; H, 6.04; F, 5.42; N, 15.99; O, 9.13
CAS #
171228-49-2
Related CAS #
Posaconazole-d5;1217785-83-5;Posaconazole-d4;1133712-26-1;Posaconazole hydrate;1198769-38-8
Appearance
Solid powder
SMILES
FC1=CC=C([C@@]2(CN3C=NC=N3)C[C@H](COC4=CC=C(N5CCN(C6=CC=C(N7C=NN([C@@H](CC)[C@H](C)O)C7=O)C=C6)CC5)C=C4)CO2)C(F)=C1
InChi Key
RAGOYPUPXAKGKH-XAKZXMRKSA-N
InChi Code
InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27+,35-,37-/m0/s1
Chemical Name
4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one
Synonyms
Posaconazole; Noxafil; SCH-56592; Schering 56592; Sch 56592; Schering 56592;
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO : 18.75~100 mg/mL ( 26.76~142.69 mM )
Solubility (In Vivo)
10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 1.88 mg/mL (2.68 mM) (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.4270 mL 7.1349 mL 14.2698 mL
5 mM 0.2854 mL 1.4270 mL 2.8540 mL
10 mM 0.1427 mL 0.7135 mL 1.4270 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.

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