1.0 2009-07-21 20:28:11 UTC 2026-05-14 16:56:11 UTC T3D2961 Ketoconazole SmallMolecule Ketoconazole is an exogenous solid with the chemical formula C26H28Cl2N4O4. Ketoconazole belongs to the piperazines, a subclass of diazinanes within the organic compounds. With an average molecular weight of 531.43 g/mol, Ketoconazole is a heavy molecule. It functions as an antifungal agent and is used industrially as an anti-dandruff agent. Recorded exposure routes include topical, oral, and inhalation. The compound is found in 26 recorded sources, including drinking water and water supply. It is present in healthcare, pharmaceuticals and veterinary products such as antibiotics, antimycotics, gynecologicals, antiadrenal preparations, and antifungals for dermatological use. Other sources include food preservation and meat processing, as well as household cleaning and consumer products such as bleaching agents, perfumes within detergents and soaps, cigar cigarettes, other smoking requisites, and non electric simulated smoking devices. It is also found in electrical and electronic equipment, including antennas, communication cables or conductors, conductors or conductive bodies characterised by the conductive materials, and electrically stimulated smoking devices or electric hearing aids. Ketoconazole targets 23 recorded proteins. It interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol, which results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of purine uptake, inhibition of yeast transformation to mycelial forms, and impairment of triglyceride and/or phospholipid biosynthesis. Additionally, it is an inhibitor of the Androgen receptor (AR), Aromatase (CYP19A1), Steroid 21-hydroxylase (CYP21A2), Aryl hydrocarbon receptor (AHR), and 18 other proteins. Drug Household Toxin Food Toxin Synthetic Toxin Organic Compound Organochloride Amine Ether Amide Drug Food Toxin Antifungal Agent Metabolite Cosmetic Toxin Household Toxin Synthetic Compound 14-alpha Demethylase Inhibitor Human Neurotoxin (+-)-cis-1-acetyl-4-(p-((2-(2,4-dichlorophenyl)-2-(imidazol-1- ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine cis-1-Acetyl-4-(4-((2-(2,4-dichlorophenyl)-2-(1H- imidazol-1-ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-ketoconazol Extina Fungarest Fungoral Ketoconazol Ketoconazolum Ketodan Ketoderm Ketoisdin Ketozole Nizoral Nizoral a-D Nizoral Cream Nizoral Shampoo Orifungal Orifungal M Panfungol Piperazine Xolegel C26H28Cl2N4O4 531.431 530.148760818 1-[4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one ketoconazole 65277-42-1 CC(=O)N1CCN(CC1)C1=CC=C(OCC2COC(CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1 InChI=1S/C26H28Cl2N4O4/c1-19(33)31-10-12-32(13-11-31)21-3-5-22(6-4-21)34-15-23-16-35-26(36-23,17-30-9-8-29-18-30)24-7-2-20(27)14-25(24)28/h2-9,14,18,23H,10-13,15-17H2,1H3 XMAYWYJOQHXEEK-UHFFFAOYSA-N Organic compounds Organoheterocyclic compounds Diazinanes Piperazines Phenylpiperazines 1,3-dioxolanes Acetamides Alkyl aryl ethers Amino acids and derivatives Aminophenyl ethers Aniline and substituted anilines Aryl chlorides Azacyclic compounds Carbonyl compounds Dialkylarylamines Dichlorobenzenes Heteroaromatic compounds Hydrocarbon derivatives Ketals N-arylpiperazines N-substituted imidazoles Organic oxides Organochlorides Organopnictogen compounds Oxacyclic compounds Phenoxy compounds Tertiary carboxylic acid amides 1,3-dichlorobenzene Acetal Acetamide Alkyl aryl ether Amine Amino acid or derivatives Aminophenyl ether Aniline or substituted anilines Aromatic heteromonocyclic compound Aryl chloride Aryl halide Azacycle Azole Benzenoid Carbonyl group Carboxamide group Carboxylic acid derivative Chlorobenzene Dialkylarylamine Ether Halobenzene Heteroaromatic compound Hydrocarbon derivative Imidazole Ketal Meta-dioxolane Monocyclic benzene moiety N-arylpiperazine N-substituted imidazole Organic nitrogen compound Organic oxide Organic oxygen compound Organochloride Organohalogen compound Organonitrogen compound Organooxygen compound Organopnictogen compound Oxacycle Phenol ether Phenoxy compound Phenylpiperazine Tertiary aliphatic/aromatic amine Tertiary amine Tertiary carboxylic acid amide Aromatic heteromonocyclic compounds N-arylpiperazine N-carbonylpiperazine a small molecule dichlorobenzene dioxolane ether imidazoles Detected and Not Quantified Exogenous Cytoplasm Membrane Ketoconazole Anti-fungal Action Pathway SMP0125162 Ketoconazole Drug Metabolism Action Pathway SMP0143456 Ketoconazole Predicted Metabolism Pathway SMP0174870 Solid White powder. melting_point 146°C solubility 0.0866 mg/L logp 4.35 logp 4.30 ALOGPS logs -4.76 ALOGPS solubility 9.31e-03 g/l ALOGPS logp 4.19 ChemAxon pka_strongest_basic 6.75 ChemAxon iupac 1-[4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one ChemAxon average_mass 531.431 ChemAxon mono_mass 530.148760818 ChemAxon smiles CC(=O)N1CCN(CC1)C1=CC=C(OCC2COC(CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1 ChemAxon formula C26H28Cl2N4O4 ChemAxon inchi InChI=1S/C26H28Cl2N4O4/c1-19(33)31-10-12-32(13-11-31)21-3-5-22(6-4-21)34-15-23-16-35-26(36-23,17-30-9-8-29-18-30)24-7-2-20(27)14-25(24)28/h2-9,14,18,23H,10-13,15-17H2,1H3 ChemAxon inchikey XMAYWYJOQHXEEK-UHFFFAOYSA-N ChemAxon polar_surface_area 69.06 ChemAxon refractivity 138.07 ChemAxon polarizability 54.83 ChemAxon rotatable_bond_count 7 ChemAxon acceptor_count 6 ChemAxon donor_count 0 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Oral (L1908) ; topical (L1908) Ketoconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone. (A1990, A1991, A1992, A1993) Hepatotoxicity, LD₅₀=86 mg/kg (orally in rat) Hepatic. Ketoconazole is partially metabolized in the liver to several inactive metabolites by oxidation and degradation of the imidazole and piperazine rings, by oxidative O-dealkylation, and by aromatic hydroxylation. (A625) Half Life: 2 hours Hepatotoxicity, LD₅₀=86 mg/kg (orally in rat) LD50: 44 mg/kg (Intravenous, Mouse) (T66) LD50: 702 mg/kg (Oral, Mouse) (T66) No indication of carcinogenicity to humans (not listed by IARC). Ketoconazole is an antifungal agent. It is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet, under the trademark name Nizoral by Johnson & Johnson. (L1908). It is used for the treatment of the following systemic fungal infections: candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. #<HealthEffect::ActiveRecord_Associations_CollectionProxy:0x00007f72254c51f0> Side effects of the potential hepatotoxicity of Ketoconazole include abdominal pain or tenderness, clay-colored stools, dark urine, decreased appetite, fever, headache, itching, loss of appetite, nausea and vomiting, skin rash, swelling of the feet or lower legs, unusual tiredness or weakness, and yellow eyes or skin. (L1536) In the event of accidental overdosage, supportive measures, including gastric lavage with sodium bicarbonate, should be employed. (L1712) DB01026 HMDB12242 3823 CHEMBL295698 43284 48339 CPD-4503 Ketoconazole KLN Ketoconazole 10933341 10451809 15737124 12476017 12480170 O'Neil MJ (ed) (2001). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc. McEvoy GK (ed) (2006). American Hospital Formulary Service - Drug Information 2006. Bethesda, MD: American Society of Health-System Pharmacists. Drugs.com: http://www.drugs.com/cons/Ketoconazole.html RxList: The Internet Drug Index (2009).: http://www.rxlist.com/ Wikipedia. Ketoconazole. Last Updated 7 December 2009.: http://en.wikipedia.org/wiki/Ketoconazole BE0000344 Inhibitory 0.038 uM BindingDB 31768 IC50 0.026 uM BindingDB 31768 IC50 0.065 uM BindingDB 31768 IC50 0.077 uM BindingDB 31768 IC50 0.078 uM BindingDB 31768 IC50 0.74 uM BindingDB 31768 IC50 0.86 uM BindingDB 31768 IC50 0.92 uM BindingDB 31768 IC50 1.1 uM BindingDB 31768 IC50 2.78 uM BindingDB 31768 IC50 2.8 uM BindingDB 31768 IC50 4.5 uM BindingDB 31768 BE0002090 Inhibitory 0.398 uM BindingDB 31768 Inhibitory 0.4 uM BindingDB 31768 Inhibitory 65 uM BindingDB 31768 IC50 0.04 uM BindingDB 8610 IC50 0.06 uM BindingDB 31768 IC50 0.8 uM BindingDB 31768 IC50 0.9 uM BindingDB 31768 IC50 1.3 uM BindingDB 31768 IC50 2.4 uM BindingDB 31768 IC50 3 uM BindingDB 31768 IC50 3.98 uM BindingDB 50004442 IC50 16 uM BindingDB 31768 IC50 110 uM BindingDB 31768 IC50 >50 uM BindingDB 31768 BE0000875 Ketoconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone. (A365) Inhibitory 0.025 uM BindingDB 31768 Inhibitory 0.064 uM BindingDB 31768 IC50 0.19 uM BindingDB 31768 Dissociation 0.11 uM BindingDB 31768 Dissociation 8 uM BindingDB 31768 BE0001032 Inhibitory 1.2 uM BindingDB 31768 IC50 1 uM BindingDB 31768 IC50 1.2 uM BindingDB 8610 IC50 4.8 uM BindingDB 31768 IC50 5.6 uM BindingDB 8610 IC50 13 uM BindingDB 31768 IC50 23.4 uM BindingDB 8610 IC50 53.4 uM BindingDB 8610 BE0002250 Inhibitory 0.024 uM BindingDB 8610 Inhibitory 0.032 uM BindingDB 8610 IC50 0.126 uM BindingDB 31768 IC50 0.312 uM BindingDB 31768 IC50 0.52 uM BindingDB 31768 BE0003542 IC50 0.067 uM BindingDB 8610 IC50 0.081 uM BindingDB 8610 BE0004883 BE0000731 IC50 0.127 uM BindingDB 31768 BE0002638 IC50 0.072 uM BindingDB 8610 IC50 0.57 uM BindingDB 50004442 IC50 1.26 uM BindingDB 31768 BE0004873 IC50 4.46 uM BindingDB 50004442 IC50 9.01 uM BindingDB 31768 BE0004884 BE0000443 Inhibitory 0.053 uM BindingDB 8610 Inhibitory 0.092 uM BindingDB 8610 BE0000132 BE0000703 IC50 65.4 uM BindingDB 8610 BE0000589 IC50 >150 uM BindingDB 31768 BE0003848 BE0000090 BE0003644 IC50 264 uM BindingDB 31768 BE0000749 AC50 0.36 uM NVS_TR_hSERT Novascreen BE0003721 AC50 1.48 uM ATG_Ahr_CIS Attagene AC50 1.25 uM Tox21_AhR Tox21/NCGC BE0000956 AC50 1.79 uM ATG_PXR_TRANS Attagene BE0001777 AC50 9.07 uM NVS_NR_hFXR_Antagonist Novascreen AC50 3.97 uM OT_SRC1_SRC1FXR_0480 Odyssey Thera AC50 3.21 uM OT_SRC1_SRC1FXR_1440 Odyssey Thera BE0005532 AC50 4.80 uM ATG_RORE_CIS Attagene BE0005534 AC50 5.98 uM NVS_ENZ_hSIRT2 Novascreen BE0000779 AC50 7.14 uM ATG_VDRE_CIS Attagene BE0005540 AC50 7.15 uM ATG_SREBP_CIS Attagene BE0000690 BE0000233