Posaconazole

SKU: orb1300976

Description

Posaconazole is a potent small molecule inhibitor of sterol 14α-demethylase, exhibiting an IC50 of 0.25 nM. This antifungal agent is widely used in research to study fungal pathogenesis and treatment, with applications in both in vitro assays and in vivo animal models of infection.

Research Area

Infectious Disease & Virology

Key Properties

• CAS Number: 171228-49-2
• MW: 700.78
• Purity: 99.72%
• Formula: C₃₇H₄₂F₂N₈O₄
• SMILES: C([C@@]1(C[C@H](COC2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)N5C(=O)N([C@H]([C@H](C)O)CC)N=C5)CO1)C6=C(F)C=C(F)C=C6)N7C=NC=N7
• Target: Parasite,Antifungal
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:245 mg/mL (349.61 mM)

Bioactivity

• Target IC50:
  C14ɑ demethylase:0.25 nM
• In Vivo:
  Posaconazole exhibits enhanced efficacy against clinically relevant intracellular, non-flagellated parasitic forms. Its minimum inhibitory concentration (MIC) and IC50 are 3 nM and 0.25 nM, respectively. Posaconazole is active against strains of Candida and Aspergillus that are resistant to fluconazole, voriconazole, and amphotericin B, showing superior effectiveness compared to other triazole antifungal agents. It synergizes with amiodarone and disrupts the internal calcium (Ca2+) homeostasis in T. cruzi. Additionally, posaconazole demonstrates a dose-dependent effect on the proliferation of the extracellular (pre-flagellar) stage, with an MIC of 20 nM and an IC50 of 14 nM.
• In Vitro:
  The bioavailability of Posaconazole is significantly increased by food intake, especially a high-fat diet. When consumed with high-fat and non-fat meals, the systemic exposure to Posaconazole is respectively quadrupled and increased by 2.6 times. Administration of Posaconazole (≥15 mg/kg, b.i.d) can extend the lifespan of mice and reduce tissue burden. Used alone in infected animals, Amiodarone reduces parasitemia and increases the survival rate to 60% at 60 days (compared to 0% in untreated controls), demonstrating this effect. When used in combination, Posaconazole and Amiodarone can delay the progression of parasitemia. This suggests that Posaconazole and Amiodarone may offer an effective, low-side-effect treatment against T. cruzi. When Posaconazole is taken fasting with Boost Plus, there is an increase in drug exposure.
• Cell Research:
  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 °

Storage & Handling

• Storage: keep away from direct sunlight,keep away from moisture,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

POS, Posaconazole, SCH 56592, SCH56592, SCH-56592, inhibit, Inhibitor, Fungal, Antifungal

Compound Identifiers

PubChem CID

468595