POSACONAZOLE

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Trade Names
Synonyms
Status
Molecule Category Free-form
ATC J02AC04
UNII 6TK1G07BHZ

Structure

InChI Key RAGOYPUPXAKGKH-XAKZXMRKSA-N
Smiles CC[C@@H]([C@H](C)O)n1ncn(-c2ccc(N3CCN(c4ccc(OC[C@@H]5CO[C@@](Cn6cncn6)(c6ccc(F)cc6F)C5)cc4)CC3)cc2)c1=O
InChI
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

Physicochemical Descriptors

Property Name Value
Molecular Formula C37H42F2N8O4
Molecular Weight 700.79
AlogP 4.57
Hydrogen Bond Acceptor 12.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 12.0
Polar Surface Area 115.7
Molecular species NEUTRAL
Aromatic Rings 5.0
Heavy Atoms 51.0

Bioactivity

Mechanism of Action Action Reference
Cytochrome P450 51 inhibitor INHIBITOR DailyMed
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Cytochrome P450 Cytochrome P450 family 11 Cytochrome P450 family 11B Cytochrome P450 11B1
- 310 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 11 Cytochrome P450 family 11B Cytochrome P450 11B2
- 21 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 17 Cytochrome P450 family 17A Cytochrome P450 17A1
- 42-1800 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 19 Cytochrome P450 family 19A Cytochrome P450 19A1
- 8400 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2C Cytochrome P450 2C9
- 7200 - - -
Enzyme Cytochrome P450 Cytochrome P450 family 3 Cytochrome P450 family 3A Cytochrome P450 3A4
- 50-672 - - 98
Enzyme Cytochrome P450 Cytochrome P450 family 3 Cytochrome P450 family 3A Cytochrome P450 3A5
- - - - 98
Enzyme Cytochrome P450 Cytochrome P450 family 51 Cytochrome P450 family 51A Cytochrome P450 51A1
- - 131 - 93
Enzyme Oxidoreductase
- 48 18-60 - -
Enzyme
- 50-672 18-60 - 93
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel
- - - - 15
Transporter Primary active transporter ATP-binding cassette ABCB subfamily
- 8100 - - -
Assay Description Organism Bioactivity Reference
Antiprotozoal activity against Trypanosoma cruzi epimastigotes Trypanosoma cruzi 14.0 nM
Antiprotozoal activity against Trypanosoma cruzi amastigotes Trypanosoma cruzi 0.25 nM
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen amastigotes expressing beta-galactosidase in mouse 3T3 fibroblast after 7 days by alamar blue assay Trypanosoma cruzi 0.3 nM
Inhibition of human recombinant CYP3A4 Homo sapiens 350.0 nM
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen infected in mouse 3T3 cells Trypanosoma cruzi 0.3 nM
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen amastigotes infected in rat 3T3 cells after 7 days by alamar blue assay Trypanosoma cruzi 0.3 nM
Inhibition of human recombinant CYP3A4 Homo sapiens 82.0 nM
Antitrypanosomal activity against Trypanosoma cruzi CA-I/72 infected in BESM cells measured after 88 hrs postinfection by HTS assay Trypanosoma cruzi 200.0 nM
Antitrypanosomal activity against Trypanosoma cruzi Sylvio-X10/7 infected in BESM cells measured after 88 hrs postinfection by HTS assay Trypanosoma cruzi 80.0 nM
Antitrypanosomal activity against Trypanosoma cruzi PSD-I infected in BESM cells measured after 88 hrs postinfection by HTS assay Trypanosoma cruzi 130.0 nM
Antifungal activity against inoculum of 1x10'4 conidia/ml Fusarium solani isolate 95-2478 after 24 hrs by XTT assay Fusarium solani 1.7 ug.mL-1
Antifungal activity against inoculum of 1x10'4 conidia/ml Fusarium solani isolate 95-2478 after 48 hrs by XTT assay Fusarium solani 4.7 ug.mL-1
Antifungal activity against inoculum of 1x10'5 conidia/ml Fusarium solani isolate 95-2478 after 24 hrs by XTT assay Fusarium solani 7.2 ug.mL-1
Antifungal activity against inoculum of 1x10'5 conidia/ml Fusarium solani isolate 95-2478 after 48 hrs by XTT assay Fusarium solani 8.0 ug.mL-1
Binding affinity to Aspergillus fumigatus AF293 sterol 14-alpha demethylase isoenzyme B expressed in Escherichia coli assessed as tight binding affinity constant Aspergillus fumigatus 73.0 nM
Inhibition of CYP3A4/6 in human liver microsomes at 20 uM Homo sapiens 98.0 %
Binding affinity to Trypanosoma cruzi recombinant full length CYP51 by spectrophotometric analysis Trypanosoma cruzi 60.0 nM
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen TcVI extracellular trypomastigotes forms transfected with beta-galactosidase gene infected in rat L6 cells assessed as inhibition of parasite growth after 4 days Trypanosoma cruzi 0.7 nM
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen infected in 3T3 cells after 7 days by beta-galactosidase assay Trypanosoma cruzi 1.0 nM
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen 6 amastigotes infected in rat L6 cells after 96 hrs by colorimetric method Trypanosoma cruzi 1.0 nM
Inhibition of CYP3A4 in human hepatocytes using testosterone as substrate by HPLC/MS/MS method Homo sapiens 50.0 nM
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen trypomastigotes expressing green florescent protein infected in cardiomyocytes assessed as inhibition of parasite growth after 72 hrs by fluorescence microscopy Trypanosoma cruzi 5.0 nM
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen trypomastigotes expressing green florescent protein infected in cardiomyocytes assessed as inhibition of parasite growth at 10 nM after 72 hrs by fluorescence microscopy Trypanosoma cruzi 64.0 %
Inhibition of hedgehog pathway in mouse C3H10T1/2 cells assessed as downregulation of Gli1 mRNA expression after 24 hrs by qPCR method Mus musculus 140.0 nM
Inhibition of hedgehog pathway in mouse ASZ cells assessed as downregulation of Gli1 mRNA expression after 48 hrs by qPCR method Mus musculus 540.0 nM
Inhibition of CYP3A4 in human hepatocyte microsomes using testosterone substrate by HPLC/MS/MS method Homo sapiens 75.0 nM
Inhibition of CYP11B1 in human hepatocyte microsomes using deoxycortisol substrate by HPLC/MS/MS method Homo sapiens 310.0 nM
Inhibition of CYP11B2 in human hepatocyte microsomes using deoxycorticosteroid substrate by HPLC/MS/MS method Homo sapiens 21.0 nM
Inhibition of CYP17 lyase in human hepatocyte microsomes using 17a-hydroxypregnenolone substrate by HPLC/MS/MS method Homo sapiens 42.0 nM
Inhibition of Candida albicans CYP51 assessed as reduction in [3-3H]lanosterol 14alpha-demethylation at 0.75 uM preincubated for 60 secs followed by NADPH addition measured after 60 mins by RP-HPLC analysis relative to control Candida albicans 98.0 %
Inhibition of Aspergillus fumigatus CYP51 assessed as reduction in [3-3H]eburicol 14alpha-demethylation at 0.75 uM preincubated for 60 secs followed by NADPH addition measured after 60 mins by RP-HPLC analysis relative to control Aspergillus fumigatus 93.0 %
Binding affinity to Candida albicans CYP51 by spectral titration method Candida albicans 81.0 nM
Binding affinity to Aspergillus fumigatus CYP51 by spectral titration method Aspergillus fumigatus 131.0 nM
Inhibition of recombinant Trypanosoma cruzi Tulahuen CYP51 expressed in Escherichia coli JM109 cell membranes assessed as inhibition of microbe growth by fluorescence based analysis Trypanosoma cruzi 48.0 nM
Toxicity in human A549 cells assessed as reduction in cell viability incubated for 24 hrs by resazurin dye based assay Homo sapiens 37.0 ug.mL-1
Toxicity in human BEAS2B cells assessed as reduction in cell viability incubated for 24 hrs by resazurin dye based assay Homo sapiens 26.0 ug.mL-1
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens 106.34 %
Inhibition of hedgehog signaling pathway in mouse ASZ cells assessed as decrease in Gli1 mRNA expression after 48 hrs by qRT-PCR analysis Mus musculus 500.0 nM
Inhibition of CYP3A4 in human liver microsomes by LC-MS/MS analysis Homo sapiens 150.0 nM
Inhibition of human ERG expressed in CHO cells at 25 uM by electrophysiology assay relative to control Homo sapiens 14.7 %
Binding affinity to full length Trypanosoma cruzi Tulahuen C4 C-terminal His-tagged CYP51 expressed in Escherichia coli HMS174 (DE3) assessed as induction of shift in Soret band by spectrophotometry Trypanosoma cruzi 18.0 nM
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen 20A trypomastigote expressing GFP infected in BALB/c mouse cardiomyocytes assessed as reduction in parasitemia measured after 72 hrs by fluorescence assay Trypanosoma cruzi 5.0 nM
Inhibition of recombinant human CYP3A4 using Luciferin-PPXE as substrate preincubated for 10 mins followed by NADPH addition measured after 15 mins by luminometric method Homo sapiens 672.1 nM
Cytotoxicity against human HepG2 cells assessed as reduction in cell viability at 5 to 50 uM incubated for 24 hrs by XTT assay relative to control Homo sapiens 40.0 %
Cytotoxicity against human HEK293T cells assessed as reduction in cell viability at 5 to 50 uM incubated for 24 hrs by XTT assay relative to control Homo sapiens 40.0 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 24.47 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 7.61 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 6.608 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 16.69 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.88 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 1.36 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.88 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 16.69 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 1.36 %
Growth inhibiting activity of Naegleria gruberi in vitro Naegleria gruberi 84.8 %
Antitrypanosomal activity against Trypanosoma cruzi Tulahuen strain C2C4 amastigotes infected in rat 3T3 cells assessed as reduction in parasite growth incubated for 48 hrs by chlorophenol red-fl-D-galactopyranoside based colorimetric analysis Trypanosoma cruzi 1.2 nM
Inhibition of Trypanosoma cruzi Tulahuen C4 strain CYP51 expressed in Escherichia coli by fluorescence based assay Trypanosoma cruzi 5.2 nM
Inhibition of Naegleria fowleri CYP51 catalytic activity using [3-3H]sterol substrate measured after 1 hr by RP-HPLC analysis Naegleria fowleri 690.0 nM

Cross References

Resources Reference
ChEBI 64355
ChEMBL CHEMBL1397
DrugBank DB01263
DrugCentral 3483
FDA SRS 6TK1G07BHZ
KEGG D02555
PDB X2N
PubChem 468595
SureChEMBL SCHEMBL991747
ZINC ZINC000003938482
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