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Compound Detail

CHEMBL638

VORICONAZOLE
💊 Approved Drug
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💊 Approved Drug
C[C@@H](c1ncncc1F)[C@](O)(Cn1cncn1)c1ccc(F)cc1F

Basic Information

ChEMBL ID CHEMBL638
Name VORICONAZOLE
Phase Approved
Structure Type MOL
InChI Key BCEHBSKCWLPMDN-MGPLVRAMSA-N
Therapeutic ✓ Yes

Known Names

NSC-759888 UK-109,496 UK-109496 Vfend Voriconazol Voriconazole Voriconazole accord Voriconazole hikma (previously voriconazole hospira)
18
Targets
70
Activities
3
Assay Types
30
PK Parameters
20
Publications
8
Known Names
20
Indications
1
Mechanisms

Molecular Properties

349.3
MW (Da)
2.18
ALogP
6
HBA
1
HBD
76.7
PSA (Ų)
0.76
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2002
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral Parenteral
USAN Stem -conazole
USAN Year 1999

Extended Properties

Molecular Formula C16H14F3N5O
MW 349.32
Aromatic Rings 3
Heavy Atoms 25
NP-Likeness -0.76

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Cytochrome P450 51 inhibitor INHIBITOR Lanosterol 14-alpha demethylase

Indications

Aspergillosis Bacterial Infections and Mycoses Candidemia Candidiasis Fusariosis Infections Mycoses Candidiasis, Invasive Leishmaniasis Leukemia Leukemia, Myeloid, Acute Neuroaspergillosis Aspergillosis, Allergic Bronchopulmonary Myelodysplastic Syndromes Asthma Graft vs Host Disease Hematologic Neoplasms HIV Infections Leukemia, Lymphocytic, Chronic, B-Cell Neoplasms

ATC Classification

J02AC03
voriconazole
Level 1: ANTIINFECTIVES FOR SYSTEMIC USE
Level 2: ANTIMYCOTICS FOR SYSTEMIC USE

Activity Summary

IC50 43 meas. best 7.66
Kd 18 meas. best 7.3
Ki 9 meas. best 7.96

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Cholesterol 24-hydroxylase
CHEMBL4523510
Ki 7.96 7.96 11.0 1
Cholesterol 24-hydroxylase
CHEMBL4523510
IC50 7.66 7.495 22.0 2
Candida albicans
CHEMBL366
IC50 7.43 7.43 37.0 1
Cholesterol 24-hydroxylase
CHEMBL4523510
Kd 7.3 7.3 50.0 1
Lanosterol 14-alpha demethylase
CHEMBL3390824
Kd 7.25 7.25 56.0 1
Trypanosoma cruzi
CHEMBL368
IC50 7.01 5.98 96.5 2
ADMET
CHEMBL612558
IC50 6.8 5.2883 160.0 6
Lanosterol 14-alpha demethylase
CHEMBL1780
Kd 6.78 6.78 165.0 1
Cytochrome P450 2B6
CHEMBL4729
Ki 6.47 6.435 340.0 2
14-alpha sterol demethylase
CHEMBL1681624
Kd 6.37 6.37 423.0 2
Unchecked
CHEMBL612545
IC50 6.35 5.92 450.0 2
Unchecked
CHEMBL612545
Kd 6.29 5.0864 510.0 11
Lanosterol 14-alpha demethylase
CHEMBL1780
IC50 6.19 6.19 650.0 1
Cytochrome P450 3A
CHEMBL2364675
Ki 6.18 5.855 660.0 2
Cytochrome P450 2B6
CHEMBL4729
IC50 6.1 5.5157 790.0 7
ADMET
CHEMBL612558
Ki 5.81 5.81 1550.0 1
Cytochrome P450 2C9
CHEMBL3397
Ki 5.55 5.55 2800.0 1
Cytochrome P450 3A
CHEMBL2364675
IC50 5.54 5.54 2900.0 1
Sterol 14-alpha demethylase cyp51A
CHEMBL1681623
Kd 5.44 5.44 3630.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 5.44 5.014 3620.0 5
Cholesterol side-chain cleavage enzyme, mitochondrial
CHEMBL4813
Kd 5.32 5.32 4800.0 1
Cytochrome P450 2C19
CHEMBL3622
Ki 5.29 5.29 5100.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 5.28 4.96 5250.0 5
Leishmania amazonensis
CHEMBL612877
IC50 5.23 5.22 5840.0 2
Leishmania major
CHEMBL612879
IC50 5.21 5.21 6100.0 1
Leishmania donovani
CHEMBL367
IC50 5.21 5.21 6100.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 4.89 4.89 13000.0 5

Pharmacokinetic Data

Parameter Value Units Species
AUC 12900.0 ng.hr.mL-1 Homo sapiens
AUC 2900.0 ng.hr.mL-1 Homo sapiens
AUC 43000.0 ng.hr.mL-1 Homo sapiens
AUC 40500.0 ng.hr.mL-1 Homo sapiens
AUC 27400.0 ng.hr.mL-1 Homo sapiens
AUC 145.0 ng.hr.mL-1 Homo sapiens
AUC 19500.0 ng.hr.mL-1 Homo sapiens
AUC 4250.0 ng.hr.mL-1 Homo sapiens
AUC 26500.0 ng.hr.mL-1 Homo sapiens
AUC 25900.0 ng.hr.mL-1 Homo sapiens
AUC 47200.0 ng.hr.mL-1 Homo sapiens
AUC 19650.0 ng.hr.mL-1 Rattus norvegicus
AUC 22733.33 ng.hr.mL-1 Rattus norvegicus
AUC 8166.67 ng.hr.mL-1 Rattus norvegicus
AUC 8450.0 ng.hr.mL-1 Rattus norvegicus
AUC 39500.0 ng.hr.mL-1 Homo sapiens
AUC 222000.0 ng.hr.mL-1 Mus musculus
AUC 7197.0 ng.hr.mL-1 Rattus norvegicus
AUC 2527.0 ng.hr.mL-1 Rattus norvegicus
CL 0.02333 mL.min-1.kg-1 Homo sapiens
CL 4.232 mL.min-1.kg-1 Homo sapiens
CL 8.3 mL.min-1.kg-1 Homo sapiens
CL 3.6 L/hr Homo sapiens
CL 4.0 L/hr Homo sapiens
CL 6.3 L/hr Homo sapiens
CL 3.6 L/hr Homo sapiens
CL 4.0 L/hr Homo sapiens
CL 5.6 L/hr Homo sapiens
CL 5.0 L/hr Homo sapiens
CL 4.1 L/hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Cholesterol 24-hydroxylase Ki = 11.0 nM 7.96 Inhibition of full-length recombinant human CYP46A1 assessed as reduction in cho... -
Cholesterol 24-hydroxylase IC50 = 22.0 nM 7.66 Inhibition of full-length recombinant human CYP46A1 assessed as reduction in cho... -
Candida albicans IC50 = 37.0 nM 7.43 Antifungal activity against Candida albicans assessed as reduction in intracellu... 28893470
Cholesterol 24-hydroxylase IC50 = 47.0 nM 7.33 Inhibition of full-length recombinant human CYP46A1 assessed as reduction in 25-... -
Cholesterol 24-hydroxylase Kd = 50.0 nM 7.3 Binding affinity to full-length recombinant human CYP46A1 by spectral binding st... -
Lanosterol 14-alpha demethylase Kd = 56.0 nM 7.25 Binding affinity to Aspergillus fumigatus CYP51 by spectral titration method 29894182
Trypanosoma cruzi IC50 = 96.5 nM 7.01 Antitrypanosomal activity against amastigote stage of Trypanosoma cruzi infected... 23927763
ADMET IC50 = 160.0 nM 6.8 Inhibition of CYP2B6 variant in human liver microsomes harboring CYP2B6*6/*6 gen... 22232427
Lanosterol 14-alpha demethylase Kd = 165.0 nM 6.78 Binding affinity to Candida albicans CYP51 by spectral titration method 29894182
Cytochrome P450 2B6 Ki = 340.0 nM 6.47 Inhibition of CYP2B6 in human liver microsomes assessed as bupropion 4-hydroxyla... 19029318
ADMET IC50 = 400.0 nM 6.4 Inhibition of CYP2B6 variant in human liver microsomes harboring CYP2B6*1/*1 gen... 22232427
Cytochrome P450 2B6 Ki = 400.0 nM 6.4 Inhibition of CYP2B6 in human liver microsomes assessed as efavirenz 8-hydroxyla... 19029318
14-alpha sterol demethylase Kd = 423.0 nM 6.37 Binding affinity to Aspergillus fumigatus AF293 sterol 14-alpha demethylase isoe... 20660663
14-alpha sterol demethylase Kd = 429.0 nM 6.37 Binding affinity to Aspergillus fumigatus AF293 sterol 14-alpha demethylase isoe... 20660663
Unchecked IC50 = 450.0 nM 6.35 Catalytic inhibition of Acanthamoeba castellanii CYP51 expressed in Escherichia ... 38683753
Unchecked Kd = 510.0 nM 6.29 Binding affinity to Candida albicans CYP56 by spectrophotometry 18663031
Lanosterol 14-alpha demethylase IC50 = 650.0 nM 6.19 Inhibition of Candida albicans CYP51 using lanosterol as substrate preincubated ... 39115219
Cytochrome P450 3A Ki = 660.0 nM 6.18 Competitive inhibition of CYP3A in human liver microsomes assessed as midazolam ... 19029318
Cytochrome P450 2B6 IC50 = 790.0 nM 6.1 Inhibition of CYP2B6 in human liver microsomes assessed as 8-hydroxyefavirenz 14... 19029318
Cytochrome P450 2B6 IC50 = 1190.0 nM 5.92 Inhibition of CYP2B6 in human liver microsomes assessed as bupropion 4-hydroxyla... 19029318

Literature References

PubMed DOI Target Context # Activities
- 10.5281/zenodo.13943903 ADMET 89
19223630 10.1128/aac.01543-08 NON-PROTEIN TARGET 54
20733039 10.1128/aac.00348-10 Candida albicans 44
17438048 10.1128/aac.01176-06 Sporothrix schenckii 42
26867487 10.1016/j.bmc.2016.01.058 Danio rerio 40
17178797 10.1128/aac.01095-06 THP-1 30
20385860 10.1128/aac.01599-09 Aspergillus fumigatus 30
18212093 10.1128/aac.00942-07 NON-PROTEIN TARGET 28
19470509 10.1128/aac.00293-09 Pichia kudriavzevii 28
18694951 10.1128/aac.00517-08 Saccharomyces cerevisiae 24
18056277 10.1128/aac.01070-07 Candida albicans 23
20368400 10.1128/aac.01540-09 Homo sapiens 23
17517840 10.1128/aac.00308-07 Nakaseomyces glabratus 20
20974867 10.1128/aac.01078-10 Homo sapiens 20
20547793 10.1128/aac.00303-10 Candida albicans 20
17517840 10.1128/aac.00308-07 Candida parapsilosis 20
18227186 10.1128/aac.01159-07 Candida albicans 19
19635955 10.1128/aac.00585-09 Aspergillus tubingensis 18
17664325 10.1128/aac.00929-07 Candida albicans 17
38959728 10.1016/j.ejmech.2024.116637 Saccharomyces cerevisiae 17

Data from ChEMBL 36 via Core Engine