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Compound Detail

CHEMBL157101

KETOCONAZOLE
💊 Approved Drug
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💊 Approved Drug
CC(=O)N1CCN(c2ccc(OCC3COC(Cn4ccnc4)(c4ccc(Cl)cc4Cl)O3)cc2)CC1

Basic Information

ChEMBL ID CHEMBL157101
Name KETOCONAZOLE
Phase Approved
Structure Type MOL
InChI Key XMAYWYJOQHXEEK-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Daktarin gold Daktarin intensiv Dandrazol Dandrid Extina J02AB02 Ketoconazol Ketoconazole Ketoconazole hra Ketoconazolum Ketopine Ketozole +8 more
90
Targets
507
Activities
4
Assay Types
21
PK Parameters
20
Publications
20
Known Names
20
Indications
1
Mechanisms

Molecular Properties

531.4
MW (Da)
4.21
ALogP
7
HBA
0
HBD
69.1
PSA (Ų)
0.46
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1981
Availability OTC
Chirality Racemic

Routes of Administration

Oral Topical

Flags

Black Box Warning Withdrawn Natural Product
USAN Stem -conazole
USAN Year 1978

Extended Properties

Molecular Formula C26H28Cl2N4O4
MW 531.44
Aromatic Rings 3
Heavy Atoms 36
NP-Likeness -0.77

Mechanism of Action

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

Indications

Adrenal Gland Diseases Blastomycosis Cushing Syndrome Dermatitis, Seborrheic Tinea Tinea Pedis Acne Vulgaris Candidiasis, Vulvovaginal Dermatitis Prostatic Neoplasms, Castration-Resistant Respiratory Distress Syndrome Vaginosis, Bacterial Breast Neoplasms Burns Hypogonadism Leukemia, Myelogenous, Chronic, BCR-ABL Positive Neoplasms Neoplasms Prostatic Neoplasms Prostatic Neoplasms

ATC Classification

D01AC08
ketoconazole
Level 1: DERMATOLOGICALS
Level 2: ANTIFUNGALS FOR DERMATOLOGICAL USE
G01AF11
ketoconazole
Level 1: GENITO URINARY SYSTEM AND SEX HORMONES
Level 2: GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS
H02CA03
ketoconazole
Level 1: SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS
Level 2: CORTICOSTEROIDS FOR SYSTEMIC USE
J02AB02
ketoconazole
Level 1: ANTIINFECTIVES FOR SYSTEMIC USE
Level 2: ANTIMYCOTICS FOR SYSTEMIC USE

Drug Warnings

Withdrawn
hepatotoxicity
Liver toxicity is more frequent and severe than with other antifungal treatments; Elevated risk of early onset liver damage
Country: Guatemala; Madagascar   Year: 2011
Withdrawn
hepatotoxicity
Liver toxicity is more frequent and severe than with other antifungal treatments; Elevated risk of early onset liver damage
Country: Guatemala; Madagascar   Year: 2011
Black Box Warning
hepatotoxicity
Country: United States
Black Box Warning
cardiotoxicity
Country: United States

Activity Summary

IC50 445 meas. best 9.15
Ki 43 meas. best 8.15
Kd 15 meas. best 9.66
EC50 4 meas. best 9.52

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Gonadotropin-releasing hormone receptor
CHEMBL3066
Kd 9.66 8.3933 0.2 3
Trypanosoma cruzi
CHEMBL368
EC50 9.52 9.52 0.3 1
Unchecked
CHEMBL612545
IC50 9.15 5.7353 0.7 17
Cytochrome P450 3A4
CHEMBL340
IC50 9.05 7.2201 0.9 142
Cytochrome P450 2D6
CHEMBL289
IC50 8.73 6.558 1.9 5
Unchecked
CHEMBL612545
Kd 8.3 5.83 5.0 5
Cytochrome P450 3A4
CHEMBL340
Ki 8.15 7.6267 7.0 9
Candida albicans
CHEMBL366
IC50 8.0 7.63 10.0 4
Trichophyton rubrum
CHEMBL612649
IC50 8.0 7.85 10.0 2
Cytochrome P450 3A4/3A5
CHEMBL2111472
IC50 7.9 7.8 12.5 2
Sterol 14-alpha demethylase
CHEMBL1075110
IC50 7.85 7.85 14.0 1
Cryptococcus neoformans
CHEMBL365
IC50 7.7 7.35 20.0 2
Trypanosoma cruzi
CHEMBL368
IC50 7.64 5.5115 22.7 13
Lanosterol 14-alpha demethylase
CHEMBL3849
Ki 7.61 7.405 24.5 2
Steroid 17-alpha-hydroxylase/17,20 lyase
CHEMBL3522
IC50 7.58 6.251 26.0 39
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
CHEMBL4521
Ki 7.48 7.47 33.0 2
Homo sapiens
CHEMBL372
IC50 7.43 7.43 37.0 1
Steroid 17-alpha-hydroxylase/17,20 lyase
CHEMBL3522
Ki 7.42 7.42 38.0 2
Aromatase
CHEMBL1978
IC50 7.4 5.8267 40.0 15
Candida parapsilosis
CHEMBL612868
IC50 7.4 7.4 40.0 1
Candida tropicalis
CHEMBL612870
IC50 7.4 6.16 40.0 2
Lanosterol 14-alpha demethylase
CHEMBL4981
IC50 7.33 7.125 47.0 2
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
CHEMBL3329080
Ki 7.24 7.24 58.0 2
Lanosterol 14-alpha demethylase
CHEMBL4981
Ki 7.19 7.19 65.0 1
Cytochrome P450 11B2, mitochondrial
CHEMBL2722
IC50 7.17 6.9533 67.0 15
Liver
CHEMBL613642
IC50 7.09 7.09 80.6 1
Trichophyton mentagrophytes
CHEMBL613162
IC50 7.0 6.85 100.0 2
Lanosterol 14-alpha demethylase
CHEMBL3849
Kd 6.96 6.34 110.0 3
Cytochrome P450 11B1, mitochondrial
CHEMBL1908
IC50 6.94 6.79 116.0 11
Cytochrome P450 3A5
CHEMBL3019
IC50 6.92 6.6883 120.0 6
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
CHEMBL4521
IC50 6.9 6.426 126.0 10
Lanosterol 14-alpha demethylase
CHEMBL1780
IC50 6.89 6.89 130.0 1
Cytochrome P450 26B1
CHEMBL3713687
IC50 6.85 6.85 140.0 1
Cytochrome P450 11B1, mitochondrial
CHEMBL2927
IC50 6.82 6.52 152.0 2
Lanosterol 14-alpha demethylase
CHEMBL3849
IC50 6.72 6.72 190.0 1
Cytochrome P450 7A1
CHEMBL2339
IC50 6.71 6.165 195.0 2
Plasmodium falciparum
CHEMBL364
IC50 6.7 5.4111 200.0 9
Steroid 17-alpha-hydroxylase/17,20 lyase
CHEMBL4430
IC50 6.69 5.5678 206.0 18
Sodium-dependent serotonin transporter
CHEMBL228
Ki 6.55 6.55 282.0 1
Heme oxygenase 1
CHEMBL5035
IC50 6.52 6.52 300.0 1
Lanosterol 14-alpha demethylase
CHEMBL6066821
Kd 6.5 6.5 320.0 1
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
CHEMBL5993
IC50 6.47 6.47 340.0 1
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
CHEMBL3329080
IC50 6.44 6.44 360.0 2
Cytochrome P450 2A2
CHEMBL3705
IC50 6.43 6.345 369.0 2
Aromatase
CHEMBL1978
Ki 6.4 5.6633 398.1 3
Pichia kudriavzevii
CHEMBL612841
IC50 6.4 5.2 400.0 2
Sodium-dependent serotonin transporter
CHEMBL228
IC50 6.28 6.28 531.0 1
Leishmania donovani
CHEMBL367
IC50 6.26 5.4567 550.0 3
Leishmania amazonensis
CHEMBL612877
IC50 6.26 5.3217 550.0 6
Leishmania major
CHEMBL612879
IC50 6.26 6.26 550.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 16600.0 ng.hr.mL-1 Homo sapiens
AUC 11691.68 ng.hr.mL-1 Sus scrofa
AUC 6908.72 ng.hr.mL-1 Sus scrofa
AUC 16522.47 ng.hr.mL-1 Homo sapiens
Cmax 7093.93 nM Homo sapiens
Cmax 9000.0 nM Sus scrofa
Cmax 3000.0 nM Sus scrofa
Cmax 12507.0 nM Homo sapiens
Fu 0.39 - Homo sapiens
Fu 0.0068 - Rattus norvegicus
Fu 0.0374 - Rattus norvegicus
Fu 0.00345 - Rattus norvegicus
Fu 0.00933 - Rattus norvegicus
Fu 0.002 - Rattus norvegicus
Fu 0.0091 - Rattus norvegicus
T1/2 3.1 hr Sus scrofa
T1/2 4.1 hr Sus scrofa
T1/2 0.75 hr Cavia porcellus
T1/2 0.6667 hr Cavia porcellus
Tmax 0.7 hr Sus scrofa
Tmax 1.8 hr Sus scrofa

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Gonadotropin-releasing hormone receptor Kd = 0.221 nM 9.66 Dissociation constant was determined in vitro using rat pituitary membranes and ... 2549244
Trypanosoma cruzi EC50 = 0.3 nM 9.52 Antitrypanosomal activity against Trypanosoma cruzi Tulahuen amastigotes express... 19239254
Gonadotropin-releasing hormone receptor Kd = 0.375 nM 9.43 Dissociation constant was determined in vitro using rat pituitary membranes, at ... 2549244
Unchecked IC50 = 0.71 nM 9.15 Displacement of [131I]IMTO from CYP450c 11 in Wistar rat adrenal membrane 18348518
Cytochrome P450 3A4 IC50 = 0.9 nM 9.05 Inhibition of CYP3A4 (unknown origin) using vivid BOMCC as substrate 37776574
Cytochrome P450 3A4 IC50 = 1.0 nM 9.0 Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate a... 26962886
Cytochrome P450 3A4 IC50 = 1.0 nM 9.0 Inhibition of CYP3A4 (unknown origin) using DBF as substrate preincubated for 5 ... 36517209
Cytochrome P450 2D6 IC50 = 1.86 nM 8.73 Inhibition of CYP2D6 (unknown origin) using EOMCC as a substrate 35764033
Cytochrome P450 3A4 IC50 = 2.38 nM 8.62 Inhibition of CYP3A4 (unknown origin) using BOMCC as a substrate incubated for 2... 34237622
Cytochrome P450 3A4 IC50 = 4.0 nM 8.4 Inhibition of human CYP3A4 19679475
Cytochrome P450 3A4 IC50 = 4.0 nM 8.4 Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate afte... 26962886
Unchecked Kd = 5.0 nM 8.3 Binding affinity to Naegleria fowleri CYP51 expressed in Escherichia coli HMS-17... 34842434
Cytochrome P450 3A4 Ki = 7.0 nM 8.15 Inhibition of CYP3A4 activity in human liver microsomes using midazolam as a sub... 23355637
Cytochrome P450 3A4 IC50 = 7.0 nM 8.15 Inhibition of CYP3A4M in human liver microsomes using midazolam as substrate inc... 34672559
Cytochrome P450 3A4 IC50 = 7.4 nM 8.13 Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate asse... 27548392
Cytochrome P450 3A4 IC50 = 7.8 nM 8.11 Inhibition of CYP3A4 after 30 mins by fluorometric assay 21138310
Cytochrome P450 3A4 IC50 = 9.1 nM 8.04 Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate asse... 27548392
Cytochrome P450 3A4 IC50 = 9.8 nM 8.01 Inhibition of CYP3A4 activity in human liver microsomes assessed as dibenzo fluu... 23355637
Candida albicans IC50 = 10.0 nM 8.0 Antifungal activity against Candida albicans ATCC 32354 after 48 hrs by CLSI met... 18458131
Candida albicans IC50 = 10.0 nM 8.0 Antifungal activity against Candida albicans ATCC 14053 after 48 hrs by CLSI met... 18458131

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885861 Rattus norvegicus 1391
- 10.6019/CHEMBL3885881 Rattus norvegicus 1106
38888292 10.1021/acs.jmedchem.4c01057 Candida albicans 49
29648811 10.1021/acs.jmedchem.7b01729 Candida albicans 32
33316690 10.1016/j.ejmech.2020.113048 Candida albicans 32
17502416 10.1128/aac.01237-06 Candida albicans 30
18625775 10.1128/aac.00541-08 Candida albicans 28
17438048 10.1128/aac.01176-06 Sporothrix schenckii 21
37752076 10.1021/acs.jmedchem.3c01372 Candida albicans 20
18458131 10.1128/aac.01297-07 Candida albicans 20
7562925 10.1021/jm00020a005 Candida albicans 19
16472241 10.2174/1570163043334794 Hepatotoxicity 18
31732255 10.1016/j.ejmech.2019.111813 ADMET 18
20350944 10.1128/aac.01546-09 Molecular identity unknown 17
38959728 10.1016/j.ejmech.2024.116637 Saccharomyces cerevisiae 17
17360571 10.1073/pnas.0609370104 Candida parapsilosis 16
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
8027972 10.1021/jm00039a002 Candida albicans 14
27548392 10.1021/acs.jmedchem.6b00989 Cytochrome P450 3A4 14
18694951 10.1128/aac.00517-08 Saccharomyces cerevisiae 14

Data from ChEMBL 36 via Core Engine