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Compound Detail

CHEMBL1397

POSACONAZOLE
💊 Approved Drug
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💊 Approved Drug
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

Basic Information

ChEMBL ID CHEMBL1397
Name POSACONAZOLE
Phase Approved
Structure Type MOL
InChI Key RAGOYPUPXAKGKH-XAKZXMRKSA-N
Therapeutic ✓ Yes

Known Names

(-)-posaconazole Noxafil Noxafil powdermix kit Posaconazol Posaconazole Posaconazole accord Posaconazole ahcl Posaconazole sp SCH 56592 SCH-56592
20
Targets
50
Activities
3
Assay Types
30
PK Parameters
20
Publications
10
Known Names
15
Indications
1
Mechanisms

Molecular Properties

700.8
MW (Da)
4.57
ALogP
12
HBA
1
HBD
115.7
PSA (Ų)
0.20
QED
2
Ro5 Violations
12
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2005
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral Parenteral
USAN Stem -conazole
USAN Year 1999

Extended Properties

Molecular Formula C37H42F2N8O4
MW 700.79
Aromatic Rings 5
Heavy Atoms 51
NP-Likeness -0.62

Mechanism of Action

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

Indications

Aspergillosis Candidiasis Coccidioidomycosis Mycoses Neutropenia Candidiasis, Oral Leukopenia Chagas Disease Granulomatous Disease, Chronic Mucormycosis Onychomycosis Leukemia Leukemia, Myeloid, Acute Neoplasms Glioblastoma

ATC Classification

J02AC04
posaconazole
Level 1: ANTIINFECTIVES FOR SYSTEMIC USE
Level 2: ANTIMYCOTICS FOR SYSTEMIC USE

Activity Summary

IC50 35 meas. best 9.6
EC50 9 meas. best 9.52
Kd 6 meas. best 7.75

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Trypanosoma cruzi
CHEMBL368
IC50 9.6 8.8022 0.2 9
Trypanosoma cruzi
CHEMBL368
EC50 9.52 8.2813 0.3 8
Unchecked
CHEMBL612545
IC50 8.28 6.58 5.2 4
Sterol 14-alpha demethylase
CHEMBL1075110
Kd 7.75 7.485 18.0 2
Cytochrome P450 11B2, mitochondrial
CHEMBL2722
IC50 7.68 7.68 21.0 1
Steroid 17-alpha-hydroxylase/17,20 lyase
CHEMBL3522
IC50 7.38 6.565 42.0 2
Sterol 14-alpha demethylase
CHEMBL1075110
IC50 7.32 6.69 48.0 2
Cytochrome P450 3A4
CHEMBL340
IC50 7.3 6.8267 50.0 6
14-alpha sterol demethylase
CHEMBL1681624
Kd 7.14 7.14 73.0 1
Lanosterol 14-alpha demethylase
CHEMBL1780
Kd 7.09 7.09 81.0 1
Lanosterol 14-alpha demethylase
CHEMBL3390824
Kd 6.88 6.88 131.0 1
Molecular identity unknown
CHEMBL612546
IC50 6.85 6.56 140.0 2
Cytochrome P450 11B1, mitochondrial
CHEMBL1908
IC50 6.51 6.51 310.0 1
Leishmania amazonensis
CHEMBL612877
IC50 5.8 5.8 1600.0 1
SARS-CoV-2
CHEMBL4303835
IC50 5.79 5.79 1610.0 1
Sterol 14-alpha demethylase cyp51A
CHEMBL1681623
Kd 5.57 5.57 2690.0 1
7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase
CHEMBL4523494
IC50 5.42 5.42 3800.0 1
dengue virus type 2
CHEMBL613966
EC50 5.39 5.39 4100.0 1
Broad substrate specificity ATP-binding cassette transporter ABCG2
CHEMBL5393
IC50 5.22 5.22 6000.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 5.14 5.14 7200.0 1
Bile salt export pump
CHEMBL6020
IC50 5.09 5.09 8100.0 1
Aromatase
CHEMBL1978
IC50 5.08 5.08 8400.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 26740.0 ng.hr.mL-1 Homo sapiens
AUC 35444.0 ng.hr.mL-1 Homo sapiens
AUC 27784.0 ng.hr.mL-1 Homo sapiens
AUC 25507.0 ng.hr.mL-1 Homo sapiens
AUC 32963.0 ng.hr.mL-1 Homo sapiens
AUC 37924.0 ng.hr.mL-1 Homo sapiens
AUC 30091.0 ng.hr.mL-1 Homo sapiens
AUC 25107.0 ng.hr.mL-1 Homo sapiens
AUC 10200.0 ng.hr.mL-1 Mus musculus
AUC 45070.0 ng.hr.mL-1 Mus musculus
AUC 159420.0 ng.hr.mL-1 Mus musculus
AUC 296720.0 ng.hr.mL-1 Mus musculus
AUC 10.19 hr/L.kg Mus musculus
AUC 11.27 hr/L.kg Mus musculus
AUC 9.96 hr/L.kg Mus musculus
AUC 4.64 hr/L.kg Mus musculus
AUC 3630.0 ng.hr.mL-1 Homo sapiens
AUC 18600.0 ng.hr.mL-1 Homo sapiens
AUC 1760.0 ng.hr/g Homo sapiens
AUC 23400.0 ng.hr/g Homo sapiens
AUC 7260.0 ng.hr.mL-1 Homo sapiens
AUC 37200.0 ng.hr.mL-1 Homo sapiens
AUC 3520.0 ng.hr/g Homo sapiens
AUC 46800.0 ng.hr/g Homo sapiens
AUC 21900.0 ng.hr.mL-1 Homo sapiens
AUC 18300.0 ng.hr.mL-1 Homo sapiens
AUC 715000.0 ng.hr.mL-1 Homo sapiens
AUC 10441.0 ng.hr.mL-1 Homo sapiens
AUC 10866.0 ng.hr.mL-1 Homo sapiens
AUC 8030.0 ng.hr.mL-1 Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Trypanosoma cruzi IC50 = 0.25 nM 9.6 Antiprotozoal activity against Trypanosoma cruzi amastigotes 16451055
Trypanosoma cruzi EC50 = 0.3 nM 9.52 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen infected in mouse 3... 19875282
Trypanosoma cruzi EC50 = 0.3 nM 9.52 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen amastigotes infecte... 20429511
Trypanosoma cruzi EC50 = 0.3 nM 9.52 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen amastigotes express... 19239254
Trypanosoma cruzi IC50 = 0.7 nM 9.15 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen TcVI extracellular ... 23462713
Trypanosoma cruzi IC50 = 1.0 nM 9.0 Antitrypanosomal activity against intracellular Trypanosoma cruzi amastigote inf... 36459758
Trypanosoma cruzi IC50 = 1.0 nM 9.0 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen 6 amastigotes infec... 24304150
Trypanosoma cruzi IC50 = 1.2 nM 8.92 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen strain C2C4 amastig... 33007723
Trypanosoma cruzi IC50 = 2.0 nM 8.7 Antitrypanosomal activity against intracellular Trypanosoma cruzi amastigote inf... 36459758
Trypanosoma cruzi EC50 = 1.995 nM 8.7 Antitrypanosomal activity against Trypanosoma cruzi Silvio X10/7 trypomastigotes... 28844141
Trypanosoma cruzi IC50 = 2.0 nM 8.7 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen amastigotes infecte... 36111399
Trypanosoma cruzi EC50 = 5.0 nM 8.3 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen trypomastigotes exp... 25033013
Trypanosoma cruzi IC50 = 5.0 nM 8.3 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen 20A trypomastigote ... 31706668
Unchecked IC50 = 5.2 nM 8.28 Inhibition of Trypanosoma cruzi Tulahuen C4 strain CYP51 expressed in Escherichi... 33007723
Trypanosoma cruzi IC50 = 14.0 nM 7.85 Antiprotozoal activity against Trypanosoma cruzi epimastigotes 16451055
Sterol 14-alpha demethylase Kd = 18.0 nM 7.75 Binding affinity to full length Trypanosoma cruzi Tulahuen C4 C-terminal His-tag... 31706668
Cytochrome P450 11B2, mitochondrial IC50 = 21.0 nM 7.68 Inhibition of CYP11B2 in human hepatocyte microsomes using deoxycorticosteroid s... 28651982
Steroid 17-alpha-hydroxylase/17,20 lyase IC50 = 42.0 nM 7.38 Inhibition of CYP17 lyase in human hepatocyte microsomes using 17a-hydroxypregne... 28651982
Sterol 14-alpha demethylase IC50 = 48.0 nM 7.32 Inhibition of recombinant Trypanosoma cruzi Tulahuen CYP51 expressed in Escheric... 29501946
Cytochrome P450 3A4 IC50 = 50.0 nM 7.3 Inhibition of CYP3A4 in human hepatocytes using testosterone as substrate by HPL... 24948565

Literature References

PubMed DOI Target Context # Activities
19704132 10.1128/aac.00862-09 Aspergillus fumigatus 200
20145077 10.1128/aac.01463-09 Rhizopus arrhizus 166
19075045 10.1128/aac.01034-08 Homo sapiens 110
19786600 10.1128/aac.01031-09 Nakaseomyces glabratus 94
19841151 10.1128/aac.01136-09 Candida tropicalis 64
20805397 10.1128/aac.00786-10 Cunninghamella bertholletiae 60
19223630 10.1128/aac.01543-08 NON-PROTEIN TARGET 54
20065054 10.1128/aac.01445-09 Fusarium solani 48
17101682 10.1128/aac.00472-06 Homo sapiens 40
19786600 10.1128/aac.01031-09 Candida albicans 37
20516276 10.1128/aac.01396-09 ADMET 34
20385860 10.1128/aac.01599-09 Aspergillus fumigatus 30
19029316 10.1128/aac.00663-08 ADMET 28
18212093 10.1128/aac.00942-07 NON-PROTEIN TARGET 28
19917751 10.1128/aac.00931-09 Mus musculus 28
18056279 10.1128/aac.01447-07 Nakaseomyces glabratus 28
19786600 10.1128/aac.01031-09 Pichia kudriavzevii 27
28395217 10.1016/j.ejmech.2017.03.075 Unchecked 24
26592740 10.1021/acs.jmedchem.5b01375 Candida albicans 21
19433558 10.1128/aac.01178-08 Homo sapiens 20

Data from ChEMBL 36 via Core Engine