Posaconazole

Synonyms: SCH 56592, POS

Posaconazole is an inhibitor primarily of CYP3A4, but it does not inhibit the activity of other CYP enzymes; Also an inhibitor of sterol C14ɑ demethylase inhibitor with IC50 of 0.25 μM. Posaconazole has a median terminal elimination half-life of 15-35 hours.

Posaconazole Chemical Structure

Posaconazole Chemical Structure

CAS: 171228-49-2

Selleck's Posaconazole has been cited by 27 Publications

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Purity & Quality Control

Batch: Purity: 99.97%
99.97

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Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human hepatocytes Function assay Inhibition of CYP3A4 in human hepatocytes using testosterone as substrate by HPLC/MS/MS method, IC50=0.05 μM 24948565
3T3 Antitrypanosomal assay Antitrypanosomal activity against Trypanosoma cruzi Tulahuen infected in mouse 3T3 cells, EC50=0.0003μM 19875282
BESM Function assay 5 uM 72 hrs Inhibition of sterol 14-alpha-demethylase in Trypanosoma cruzi epimastigotes infected in BESM cells assessed as accumulation of lanosterol and eburicol precursors at 5 uM after 72 hrs 20385875
BESM Function assay 5 uM 72 hrs Inhibition of sterol 14-alpha-demethylase in Trypanosoma cruzi epimastigotes infected in BESM cells assessed as reduction in episterol content at 5 uM after 72 hrs 20385875
BESM Function assay 5 uM 72 hrs Inhibition of sterol 14-alpha-demethylase in Trypanosoma cruzi epimastigotes infected in BESM cells assessed as reduction in fecosterol content at 5 uM after 72 hrs 20385875
BESM Function assay 5 uM 72 hrs Inhibition of sterol 14-alpha-demethylase in Trypanosoma cruzi amastigotes infected in BESM cells assessed as accumulation of lanosterol and eburicol precursors at 5 uM after 72 hrs 20385875
BESM Function assay 5 uM 72 hrs Inhibition of sterol 14-alpha-demethylase in Trypanosoma cruzi amastigotes infected in BESM cells assessed as reduction in episterol content at 5 uM after 72 hrs 20385875
BESM Function assay 5 uM 72 hrs Inhibition of sterol 14-alpha-demethylase in Trypanosoma cruzi amastigotes infected in BESM cells assessed as reduction in fecosterol content at 5 uM after 72 hrs 20385875
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 20429511
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 20547819
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 20547819
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 20547819
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 23462713
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 24120539
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 24304150
C2C12 Function assay 100 nM 24 hrs Inhibition of sterol biosynthesis in Trypanosoma cruzi CAI/72 amastigotes infected in mouse C2C12 cells assessed as increase in lanosterol level at 100 nM incubated for 24 hrs by GC-MS method 25393646
C2C12 Function assay 100 nM 24 hrs Inhibition of sterol biosynthesis in Trypanosoma cruzi CAI/72 amastigotes infected in mouse C2C12 cells assessed as increase in eburicol level at 100 nM incubated for 24 hrs by GC-MS method 25393646
C2C12 Function assay 100 nM 24 hrs Inhibition of sterol biosynthesis in Trypanosoma cruzi CAI/72 amastigotes infected in mouse C2C12 cells assessed as reduction in episterol level at 100 nM incubated for 24 hrs by GC-MS method 25393646
C2C12 Function assay 100 nM 24 hrs Inhibition of sterol biosynthesis in Trypanosoma cruzi CAI/72 amastigotes infected in mouse C2C12 cells assessed as reduction in fecosterol level at 100 nM incubated for 24 hrs by GC-MS method 25393646
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 27014922
ASZ Function assay 48 hrs Inhibition of hedgehog pathway in mouse ASZ cells assessed as downregulation of Gli1 mRNA expression after 48 hrs by qPCR method, IC50=0.54μM 27014922
MERP MB Antiproliferative assay 48 hrs Antiproliferative activity against mouse MERP MB cells assessed as cell growth inhibition using methyl-[3H]thymidine after 48 hrs by liquid scintillation spectrophotometry, GI50=1.5μM 27014922
J774 Antileishmanial assay 72 hrs Antileishmanial activity against Leishmania amazonensis infected in mouse J774 cells after 72 hrs using 2 hrs parasite exposed mouse J774 cells, IC50=1.6μM 27048943
ASZ Function assay 48 hrs Inhibition of hedgehog signaling pathway in mouse ASZ cells assessed as decrease in Gli1 mRNA expression after 48 hrs by qRT-PCR analysis, IC50=0.5μM 30529635
Ptch-CKO Function assay Inhibition of hedgehog signaling pathway in hedgehog-dependent mouse Ptch-CKO cells assessed as inhibition of cell growth, GI50=1.5μM 30529635
Caco2 Function assay Substrate activity at P-gp in human Caco2 cells by LC-MS/MS analysis 30529635
Vero Antiviral assay Antiviral activity against DENV2 16881 infected in African green monkey Vero cells by qRT-PCR analysis, EC50=4.1μM 31128447
Caco-2 Function assay 48 hrs Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging, IC50=1.61μM ChEMBL
Caco-2 Function assay 48 hrs Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay, CC50=14.64μM ChEMBL
Click to View More Cell Line Experimental Data

Biological Activity

Description Posaconazole is an inhibitor primarily of CYP3A4, but it does not inhibit the activity of other CYP enzymes; Also an inhibitor of sterol C14ɑ demethylase inhibitor with IC50 of 0.25 μM. Posaconazole has a median terminal elimination half-life of 15-35 hours.
Features Currently the most advanced candidate for the treatment of Chagas disease.
Targets
lanosterol 14α-demethylase [1] CYP3A4 [6]
In vitro
In vitro

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. [1] 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. [2]

Cell Research Cell lines Epimastigote form of T. cruzi amastigotes
Concentrations 0 nM -4 nM
Incubation Time 96 hours
Method

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 Ringer's 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.

Experimental Result Images Methods Biomarkers Images PMID
Western blot Wee1 / c-Myc / Cyclin B1 / Cdc25C / Bcl-2 / Bax / p21 / Survivin 28383032
Growth inhibition assay Cell proliferation 28383032
In Vivo
In 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. [1] 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. [3] Posaconazole and Amiodarone may constitute an effective anti-T. cruzi therapy with low side effect. [4] At twice-daily doses of ≥15 mg/kg of body weight, Posaconazole prolongs the survival of the mice and reduces tissue burden. [5]

Animal Research Animal Models Female NMRI−IVIC mice with acute Chagas
Dosages 20 mg/kg/d
Administration Oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06158360 Recruiting
Thyroid Cancer
Ilsan Cha hospital
January 1 2024 --
NCT05617638 Not yet recruiting
Pain
Hospital Israelita Albert Einstein|Beneficência Portuguesa de São Paulo
January 2024 Not Applicable
NCT05845359 Withdrawn
Bariatric Surgery Candidate
Montefiore Medical Center
September 2023 Phase 4
NCT05839327 Not yet recruiting
COVID-19 Post-Intensive Care Syndrome
Hospital Sao Domingos
June 1 2023 --
NCT05544019 Recruiting
Mature B-Cell Neoplasm|Non Hodgkin Lymphoma|DLBCL|Waldenstrom Macroglobulinemia|MALT Lymphoma|Follicular Lymphoma|Pediatric-Type Follicular Lymphoma|IRF4 Gene Rearrangement|EBV-Positive DLBCL Nos|Burkitt Lymphoma|Plasmablastic Lymphoma|High-grade B-cell Lymphoma|Primary Cutaneous Follicle Center Lymphoma|Primary Effusion Lymphoma|Mantle Cell Lymphoma|DLBCL Germinal Center B-Cell Type|Primary Mediastinal Large B Cell Lymphoma|T-Cell/Histiocyte Rich Lymphoma|ALK-Positive Large B-Cell Lymphoma|Primary Cutaneous Diffuse Large B-Cell Lymphoma|Splenic Marginal Zone Lymphoma|Chronic Lymphocytic Leukemia|Nodal Marginal Zone Lymphoma|HHV8-Positive DLBCL Nos|Lymphoplasmacytic Lymphoma|Duodenal-Type Follicular Lymphoma
Schrödinger Inc.
April 10 2023 Phase 1

Chemical Information & Solubility

Molecular Weight 700.78 Formula

C37H42F2N8O4

CAS No. 171228-49-2 SDF Download Posaconazole SDF
Smiles CCC(C(C)O)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OCC5CC(OC5)(CN6C=NC=N6)C7=C(C=C(C=C7)F)F
Storage (From the date of receipt)

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DMSO : 100 mg/mL ( (142.69 mM); Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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