Identification

Name
Ketoconazole
Accession Number
DB01026  (APRD00401)
Type
Small Molecule
Groups
Approved, Investigational
Description

Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. It is a racemate consisting of equimolar amounts of (2R,4S)- and (2S,4R)-ketoconazole with the chiral centers on the acetal ring.

Structure
Thumb
Synonyms
  • Ketoconazol
  • Ketoconazole
  • Ketoconazolum
  • Ketozole
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ExtinaAerosol, foam20 mg/1gTopicalPrestium Pharma, Inc.2014-01-10Not applicableUs
ExtinaAerosol, foam20 mg/1gTopicalMylan Pharmaceuticals2007-06-12Not applicableUs
ExtinaAerosol, foam20 mg/1gTopicalStiefel Laboratories, Inc.2007-07-012014-06-30Us
Ketoderm Cream 2%Cream2 %TopicalTaropharma, A Division Of Taro Pharmaceuticals Inc.2002-05-23Not applicableCanada
NizoralShampoo20 mg/1mLTopicalJanssen Pharmaceuticals1990-08-31Not applicableUs
NizoralShampoo20 mg/1mLTopicalA S Medication Solutions1990-08-31Not applicableUs
NizoralShampoo20 mg/1mLTopicalPhysicians Total Care, Inc.1994-04-132011-06-30Us
NizoralShampoo20 mg/1mLTopicalMc Neil Consumer Healthcare Div. Mc Neil Ppc, Inc1990-08-312010-11-30Us
NizoralTablet200 mg/1OralJanssen Pharmaceuticals1981-06-122007-06-30Us
NizoralTablet200 mg/1OralPhysicians Total Care, Inc.1991-07-312007-12-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-ketoconazoleTablet200 mgOralApotex Corporation1998-02-03Not applicableCanada
KetoconazoleTablet200 mg/1Oralbryant ranch prepack1999-06-15Not applicableUs
KetoconazoleTablet200 mg/1OralRebel Distributors1999-06-15Not applicableUs
KetoconazoleTablet200 mg/1OralRemedy Repack2013-03-152013-08-05Us
KetoconazoleCream20 mg/1gTopicalRemedy Repack2013-06-042014-06-04Us
KetoconazoleTablet200 mg/1OralMutual Pharmaceutical1999-06-152011-09-30Us
KetoconazoleTablet200 mg/1OralApotex Corporation2002-01-102012-04-01Us
KetoconazoleCream20 mg/1TopicalRemedy Repack2013-02-082014-04-02Us
KetoconazoleTablet200 mg/1OralPhysicians Total Care, Inc.2004-05-24Not applicableUs54868 507120180907 15195 11k1lk8
KetoconazoleCream20 mg/1gTopicalNucare Pharmaceuticals,inc.2002-12-18Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nizoral - 2%Shampoo2 %TopicalJohnson & Johnson1990-12-30Not applicableCanada
Nizoral A-DShampoo10 mg/1mLTopicalJohnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division1999-04-01Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
KetoconKetoconazole (20 mg/1g) + Hydrocortisone (10 mg/1g)KitTiber Laboratories, LLC2011-04-062012-06-30Us
International/Other Brands
Extina / Fungarest (Janssen-Cilag) / Fungoral (Johnson & Johnson) / Ketoderm (Hessel) / Ketoisdin (Isdin) / Ketozole (Ranbaxy) / Nizoral / Nizoral a-D / Nizoral Cream (Ortho-McNeil) / Nizoral Shampoo (Ortho-McNeil) / Orifungal (Janssen) / Orifungal M (Janssen) / Panfungol (Esteve) / Xolegel
Categories
UNII
R9400W927I
CAS number
65277-42-1
Weight
Average: 531.431
Monoisotopic: 530.148760818
Chemical Formula
C26H28Cl2N4O4
InChI Key
XMAYWYJOQHXEEK-UHFFFAOYSA-N
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
IUPAC Name
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
SMILES
CC(=O)N1CCN(CC1)C1=CC=C(OCC2COC(CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1

Pharmacology

Indication

For the treatment of the following systemic fungal infections: candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis.

Associated Conditions
Pharmacodynamics

Ketoconazole, like clotrimazole, fluconazole, itraconazole, and miconazole, is an imidazole antifungal agent.

Mechanism of action

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.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
inhibitor
Yeast
UAndrogen receptor
binder
Human
U17-hydroxylase
inhibitor
Human
USteroid 21-hydroxylase
inhibitor
Human
U11-hydroxylase
inhibitor
Human
UCytochrome P450 19A1
inhibitor
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UNuclear receptor subfamily 1 group I member 2
antagonist
Human
UNuclear receptor subfamily 1 group I member 3Not AvailableHuman
Absorption

Moderate

Volume of distribution
Not Available
Protein binding

99% (in vitro, plasma protein binding)

Metabolism

Hepatic

Route of elimination
Not Available
Half life

2 hours

Clearance
Not Available
Toxicity

Hepatotoxicity, LD50=86 mg/kg (orally in rat)

Affected organisms
  • Fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
16-BromoepiandrosteroneThe serum concentration of 16-Bromoepiandrosterone can be increased when it is combined with Ketoconazole.
19-norandrostenedioneThe serum concentration of 19-norandrostenedione can be increased when it is combined with Ketoconazole.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Ketoconazole.
5-androstenedioneThe serum concentration of 5-androstenedione can be increased when it is combined with Ketoconazole.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Ketoconazole.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Ketoconazole.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Ketoconazole.
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Ketoconazole.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Ketoconazole.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Ketoconazole.
Food Interactions
  • Avoid alcohol.
  • Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
  • Take with food.

References

Synthesis Reference

U.S. Patent 4,144,346.

General References
  1. Goeders NE, Peltier RL, Guerin GF: Ketoconazole reduces low dose cocaine self-administration in rats. Drug Alcohol Depend. 1998 Dec 1;53(1):67-77. [PubMed:10933341]
  2. Berwaerts J, Verhelst J, Mahler C, Abs R: Cushing's syndrome in pregnancy treated by ketoconazole: case report and review of the literature. Gynecol Endocrinol. 1999 Jun;13(3):175-82. [PubMed:10451809]
  3. Kazy Z, Puho E, Czeizel AE: Population-based case-control study of oral ketoconazole treatment for birth outcomes. Congenit Anom (Kyoto). 2005 Mar;45(1):5-8. [PubMed:15737124]
  4. Pierard-Franchimont C, Goffin V, Decroix J, Pierard GE: A multicenter randomized trial of ketoconazole 2% and zinc pyrithione 1% shampoos in severe dandruff and seborrheic dermatitis. Skin Pharmacol Appl Skin Physiol. 2002 Nov-Dec;15(6):434-41. [PubMed:12476017]
External Links
KEGG Drug
D00351
PubChem Compound
3823
PubChem Substance
46506746
ChemSpider
3691
BindingDB
31768
ChEBI
48339
ChEMBL
CHEMBL157101
Therapeutic Targets Database
DAP000630
PharmGKB
PA450146
HET
KTN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ketoconazole
ATC Codes
D01AC08 — KetoconazoleG01AF11 — KetoconazoleG01AF20 — Combinations of imidazole derivativesJ02AB02 — Ketoconazole
AHFS Codes
  • 84:04.08.08 — Azoles
  • 08:14.08 — Azoles
FDA label
Download (222 KB)
MSDS
Download (73.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingOtherInsulin Resistance1
0RecruitingTreatmentSkin burning sensation / Skin Rash1
1CompletedNot AvailableAlzheimer's Disease (AD) / Huntington's Disease (HD)1
1CompletedNot AvailableDrug Interactions1
1CompletedNot AvailableDrug Interactions / Healthy Volunteers / Pharmacokinetics1
1CompletedNot AvailableHCV Infections1
1CompletedNot AvailableHealthy Adult Volunteers / Pharmacokinetics of Isavuconazole / Pharmacokinetics of Ketoconazole1
1CompletedNot AvailableHealthy Volunteers5
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of Darexaban and Metabolites1
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of YM1781
1CompletedNot AvailableHealthy Volunteers / Pharmacology, Clinical1
1CompletedNot AvailableHypertension,Essential1
1CompletedNot AvailableMalignancies, Hematologic / Malignant Lymphomas1
1CompletedBasic ScienceAsthma Bronchial / AUC / Cmax / Ketoconazole / Metabolites / Pharmacokinetics / Tmax / Λz1
1CompletedBasic ScienceAlzheimer's Disease (AD)1
1CompletedBasic ScienceAutoimmune Diseases / Healthy Volunteers1
1CompletedBasic ScienceBioavailability / Drug- Drug Interactions / Healthy Volunteers1
1CompletedBasic ScienceDrug Interactions1
1CompletedBasic ScienceEffect of Ketoconazole on the PK of NBI-98854 in Healthy Subjects1
1CompletedBasic ScienceEvaluation of Pharmacokinetics of Sativex in the Absence and Presence of a CYP2C19 Inhibitor / Evaluation of Pharmacokinetics of Sativex in the Absence and Presence of a Known Inducer of CYP3A4 / Evaluation of Pharmacokinetics of Sativex in the Absence and Presence of a Potent Inhibitor of CYP3A41
1CompletedBasic ScienceHealthy Volunteers6
1CompletedBasic ScienceHuman Volunteers1
1CompletedBasic ScienceNon-Hodgkin's Lymphoma (NHL)1
1CompletedBasic ScienceObstetric Labour, Premature1
1CompletedBasic SciencePharmacokinetics1
1CompletedBasic ScienceTumors, Solid1
1CompletedDiagnosticHealthy Volunteers / Schizophrenic Disorders1
1CompletedOtherAsthma Bronchial1
1CompletedOtherDisseminated Sclerosis1
1CompletedTreatmentAdult Solid Neoplasm1
1CompletedTreatmentCancer, Advanced1
1CompletedTreatmentCancers2
1CompletedTreatmentCarcinoma NOS / Hodgkins Disease (HD) / Lymphoma, Large-Cell, Anaplastic / Neoplasms / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Malignant Lymphomas / Tumors, Solid1
1CompletedTreatmentErectile Dysfunction (ED)1
1CompletedTreatmentGastroparesis / Healthy Volunteers1
1CompletedTreatmentHealthy Male Volunteers1
1CompletedTreatmentHealthy Volunteers18
1CompletedTreatmentHealthy Volunteers / Pulmonary Disease, Chronic Obstructive2
1CompletedTreatmentHealthy Volunteers / Prophylaxis of acute chemotherapy induced nausea and vomiting2
1CompletedTreatmentMalignant Lymphomas / Nonhematologic Malignancies1
1CompletedTreatmentNeuroblastomas1
1CompletedTreatmentPharmacokinetics1
1CompletedTreatmentType 2 Diabetes Mellitus2
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific2
1RecruitingBasic ScienceHealthy Volunteers1
1RecruitingBasic ScienceSleep Restriction1
1RecruitingTreatmentNeuroblastomas / Recurrent Neuroblastoma1
1TerminatedTreatmentHealthy Volunteers1
1TerminatedTreatmentTumors1
1WithdrawnTreatmentMalignant Melanoma, Neoplasms1
1, 2Active Not RecruitingTreatmentCancer of the Ovary / Ovary Neoplasms / Primary Peritoneal Carcinoma1
1, 2CompletedTreatmentNeoplasm Metastases1
1, 2TerminatedTreatmentAdenocarcinoma, Prostate / Recurrent Prostate Carcinoma / Stage III Prostate Cancer / Stage IV Prostate Cancer1
1, 2TerminatedTreatmentProstate Cancer1
1, 2Unknown StatusTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
2Active Not RecruitingTreatmentProstate Cancer2
2CompletedTreatmentCancers / Hormonal Cycling / Prostate1
2CompletedTreatmentCancers / Prostate Neoplasms1
2CompletedTreatmentChronic Central Serous Chorioretinopathy1
2CompletedTreatmentFemur Head Necrosis / Hip Fractures / Osteoarthritis (OA)1
2CompletedTreatmentMetastatic Breast Cancer (MBC)1
2CompletedTreatmentProstate Cancer4
2CompletedTreatmentProstate Cancer / Thromboembolism1
2CompletedTreatmentTinea Pedis1
2CompletedTreatmentTumors, Solid1
2Not Yet RecruitingTreatmentPituitary gonadotropin hypofunction1
2RecruitingTreatmentProstate Cancer1
2TerminatedTreatmentAdenocarcinoma of the Prostate / Bone Metastases / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
2TerminatedTreatmentCastration-Resistant Prostate Cancer (CRPC)1
2TerminatedTreatmentGranulosa Cell Tumour of the Ovary1
2TerminatedTreatmentProstate Cancer2
2TerminatedTreatmentProstatic Neoplasms2
2Unknown StatusTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
2, 3CompletedTreatmentMinor burns1
2, 3RecruitingTreatmentMinor burns1
3CompletedTreatmentChronic Lung Diseases / Respiratory Distress Syndrome, Adult1
3CompletedTreatmentProstate Cancer4
3Not Yet RecruitingTreatmentPost - Adolescence Acne1
3Not Yet RecruitingTreatmentVaginal Candidiasis1
3RecruitingTreatmentTinea Pedis1
3TerminatedTreatmentProstate Cancer1
3TerminatedTreatmentTinea Pedis1
3Unknown StatusTreatmentBacterial Vaginosis (BV) / Candidiasis infection1
3WithdrawnTreatmentTinea Pedis1
4CompletedBasic ScienceTransplantation, Kidney1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentSeborrheic Dermatitis1
Not AvailableAvailableNot AvailableNeuroblastomas / Recurrent Neuroblastoma1
Not AvailableCompletedHealth Services ResearchGonadal Disorders / Hypogonadism / Olfacto genital dysplasia1
Not AvailableCompletedTreatmentEsophageal Candidiasis / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentSeborrheic Dermatitis1
Not AvailableRecruitingOtherHealthy Volunteers1
Not AvailableUnknown StatusTreatmentProstate Cancer1
Not AvailableWithdrawnTreatmentProstate Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Apical Pharmaceutical Corporation
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • DAVA Pharmaceuticals
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • DPT Laboratories Ltd.
  • E. Fougera and Co.
  • H.J. Harkins Co. Inc.
  • Janssen-Ortho Inc.
  • JSJ Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • McNeil Laboratories
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Nycomed Inc.
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patheon Inc.
  • Patriot Pharmaceuticals
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Perrigo Co.
  • Pharma Pac LLC
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prescript Pharmaceuticals
  • Rebel Distributors Corp.
  • Remedy Repack
  • Sandoz
  • Stiefel Labs
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • Tolmar Inc.
  • Torpharm Inc.
  • Tya Pharmaceuticals
  • United Research Laboratories Inc.
Dosage forms
FormRouteStrength
Aerosol, foamTopical20 mg/1g
Kit
Aerosol, foamTopical2 g/100g
CreamTopical20 mg/1
CreamTopical20 mg/1g
Shampoo, suspensionTopical20 mg/1mL
Shampoo, suspensionTopical20.5 mg/1mL
TabletOral200 mg/1
Kit20 mg/1g
CreamTopical2 %
ShampooTopical20 mg/1mL
ShampooTopical2 %
ShampooTopical10 mg/1mL
SuspensionOral20 mg
TabletOral200 mg
GelTopical2 %
GelTopical20 mg/1g
Prices
Unit descriptionCostUnit
Extina 2% Foam 100 gm Can375.44USD can
Extina 2% Foam 50 gm Can201.53USD can
Nizoral 2% Shampoo 120ml Bottle49.43USD bottle
Ketoconazole 2% Cream 60 gm Tube44.72USD tube
Ketoconazole 2% Cream 30 gm Tube29.43USD tube
Ketoconazole 2% Shampoo 120ml Bottle27.98USD bottle
Ketoconazole 2% Cream 15 gm Tube19.99USD tube
Ketoconazole powder15.0USD g
Nizoral 200 mg tablet4.75USD tablet
Extina 2% foam3.61USD g
Ketoconazole 200 mg tablet3.21USD tablet
Kuric 2% cream1.54USD g
Apo-Ketoconazole 200 mg Tablet1.24USD tablet
Novo-Ketoconazole 200 mg Tablet1.24USD tablet
Nu-Ketocon 200 mg Tablet1.24USD tablet
Nizoral 2% cream1.22USD g
Ketoconazole 2% cream1.1USD g
Ketoderm 2 % Cream0.35USD g
Ketoconazole 2% shampoo0.23USD ml
Nizoral a-d 1% shampoo0.07USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5456851No1994-04-072014-04-07Us
US7179475No1998-12-042018-12-04Us
US8232276No2000-11-242020-11-24Us
US8735393No1998-12-042018-12-04Us
US7553835No1998-10-192018-10-19Us
US8026238No1998-10-192018-10-19Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)146U.S. Patent 4,144,346.
water solubility0.0866 mg/LNot Available
logP4.35SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.00931 mg/mLALOGPS
logP4.3ALOGPS
logP4.19ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)6.75ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area69.06 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity138.07 m3·mol-1ChemAxon
Polarizability54.83 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.6704
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.7293
P-glycoprotein inhibitor IInhibitor0.8389
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterNon-inhibitor0.5644
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.7409
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9386
Ames testNon AMES toxic0.7003
CarcinogenicityNon-carcinogens0.8836
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.4739 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9258
hERG inhibition (predictor II)Inhibitor0.8403
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Aminophenyl ethers / Phenoxy compounds / Aniline and substituted anilines / Dialkylarylamines / Dichlorobenzenes / Alkyl aryl ethers / Ketals / Aryl chlorides / N-substituted imidazoles
show 12 more
Substituents
Phenylpiperazine / N-arylpiperazine / Aminophenyl ether / 1,3-dichlorobenzene / Phenol ether / Tertiary aliphatic/aromatic amine / Phenoxy compound / Dialkylarylamine / Aniline or substituted anilines / Alkyl aryl ether
show 34 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
N-arylpiperazine, imidazoles, ether, dioxolane, dichlorobenzene, N-carbonylpiperazine (CHEBI:48339) / a small molecule (CPD-4503)

Targets

Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name
ERG11
Uniprot ID
P10613
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
60674.965 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Agut J, Palacin C, Sacristan A, Ortiz JA: Inhibition of ergosterol synthesis by sertaconazole in Candida albicans. Arzneimittelforschung. 1992 May;42(5A):718-20. [PubMed:1627190]
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  5. Agut J, Palacin C, Salgado J, Casas E, Sacristan A, Ortiz JA: Direct membrane-damaging effect of sertaconazole on Candida albicans as a mechanism of its fungicidal activity. Arzneimittelforschung. 1992 May;42(5A):721-4. [PubMed:1627191]
  6. Croxtall JD, Plosker GL: Sertaconazole: a review of its use in the management of superficial mycoses in dermatology and gynaecology. Drugs. 2009;69(3):339-59. doi: 10.2165/00003495-200969030-00009. [PubMed:19275277]
  7. Borgers M, Degreef H, Cauwenbergh G: Fungal infections of the skin: infection process and antimycotic therapy. Curr Drug Targets. 2005 Dec;6(8):849-62. [PubMed:16375669]
  8. Warrilow AG, Martel CM, Parker JE, Melo N, Lamb DC, Nes WD, Kelly DE, Kelly SL: Azole binding properties of Candida albicans sterol 14-alpha demethylase (CaCYP51). Antimicrob Agents Chemother. 2010 Oct;54(10):4235-45. doi: 10.1128/AAC.00587-10. Epub 2010 Jul 12. [PubMed:20625155]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Eil C: Ketoconazole binds to the human androgen receptor. Horm Metab Res. 1992 Aug;24(8):367-70. [PubMed:1526623]
3. 17-hydroxylase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
References
  1. Trachtenberg J, Zadra J: Steroid synthesis inhibition by ketoconazole: sites of action. Clin Invest Med. 1988 Feb;11(1):1-5. [PubMed:2966691]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Specifically catalyzes the 21-hydroxylation of steroids. Required for the adrenal synthesis of mineralocorticoids and glucocorticoids.
Gene Name
CYP21A2
Uniprot ID
P08686
Uniprot Name
Steroid 21-hydroxylase
Molecular Weight
55886.805 Da
References
  1. Trachtenberg J, Zadra J: Steroid synthesis inhibition by ketoconazole: sites of action. Clin Invest Med. 1988 Feb;11(1):1-5. [PubMed:2966691]
5. 11-hydroxylase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
References
  1. Trachtenberg J, Zadra J: Steroid synthesis inhibition by ketoconazole: sites of action. Clin Invest Med. 1988 Feb;11(1):1-5. [PubMed:2966691]
  2. Loose DS, Kan PB, Hirst MA, Marcus RA, Feldman D: Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P450-dependent enzymes. J Clin Invest. 1983 May;71(5):1495-9. [PubMed:6304148]
Details
6. Cytochrome P450 19A1
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Weber MM, Will A, Adelmann B, Engelhardt D: Effect of ketoconazole on human ovarian C17,20-desmolase and aromatase. J Steroid Biochem Mol Biol. 1991 Feb;38(2):213-8. [PubMed:2004042]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [PubMed:15272206]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Svecova L, Vrzal R, Burysek L, Anzenbacherova E, Cerveny L, Grim J, Trejtnar F, Kunes J, Pour M, Staud F, Anzenbacher P, Dvorak Z, Pavek P: Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug Metab Dispos. 2008 Feb;36(2):339-48. Epub 2007 Nov 12. [PubMed:17998298]
  2. Li H, Redinbo MR, Venkatesh M, Ekins S, Chaudhry A, Bloch N, Negassa A, Mukherjee P, Kalpana G, Mani S: Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR. J Biol Chem. 2013 May 10;288(19):13655-68. doi: 10.1074/jbc.M113.455485. Epub 2013 Mar 22. [PubMed:23525103]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
Inverse agonist at the canonical form of the receptor. Likely an antagonist at isoform 3 of the receptor.
General Function
Zinc ion binding
Specific Function
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital re...
Gene Name
NR1I3
Uniprot ID
Q14994
Uniprot Name
Nuclear receptor subfamily 1 group I member 3
Molecular Weight
39942.145 Da
References
  1. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [PubMed:20869355]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
Found to induce the enzyme time-dependently in murine models but does not appear to have been confirmed in humans.
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Elsherbiny ME, El-Kadi AO, Brocks DR: The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci. 2008;11(1):147-59. [PubMed:18445370]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  4. Sai Y, Dai R, Yang TJ, Krausz KW, Gonzalez FJ, Gelboin HV, Shou M: Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450. Xenobiotica. 2000 Apr;30(4):327-43. [PubMed:10821163]
  5. Korashy HM, Shayeganpour A, Brocks DR, El-Kadi AO: Induction of cytochrome P450 1A1 by ketoconazole and itraconazole but not fluconazole in murine and human hepatoma cell lines. Toxicol Sci. 2007 May;97(1):32-43. Epub 2007 Feb 5. [PubMed:17283379]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Shet MS, McPhaul M, Fisher CW, Stallings NR, Estabrook RW: Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997 Nov;25(11):1298-303. [PubMed:9351907]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Draper AJ, Madan A, Parkinson A: Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. Arch Biochem Biophys. 1997 May 1;341(1):47-61. doi: 10.1006/abbi.1997.9964. [PubMed:9143352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
  2. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  3. Park JY, Kim KA, Shin JG, Lee KY: Effect of ketoconazole on the pharmacokinetics of rosiglitazone in healthy subjects. Br J Clin Pharmacol. 2004 Oct;58(4):397-402. doi: 10.1111/j.1365-2125.2004.02161.x. [PubMed:15373932]
  4. Ong CE, Coulter S, Birkett DJ, Bhasker CR, Miners JO: The xenobiotic inhibitor profile of cytochrome P4502C8. Br J Clin Pharmacol. 2000 Dec;50(6):573-80. [PubMed:11136296]
  5. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Park JY, Kim KA, Shin JG, Lee KY: Effect of ketoconazole on the pharmacokinetics of rosiglitazone in healthy subjects. Br J Clin Pharmacol. 2004 Oct;58(4):397-402. doi: 10.1111/j.1365-2125.2004.02161.x. [PubMed:15373932]
  2. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  3. McKillop D, Wild MJ, Butters CJ, Simcock C: Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53. doi: 10.1080/004982598239092 . [PubMed:9764927]
  4. Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM: Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab Dispos. 2002 Mar;30(3):314-8. [PubMed:11854151]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  2. Emoto C, Murase S, Sawada Y, Jones BC, Iwasaki K: In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: a comparison with SKF-525A and ketoconazole. Drug Metab Pharmacokinet. 2003;18(5):287-95. [PubMed:15618748]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Emoto C, Murase S, Sawada Y, Jones BC, Iwasaki K: In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: a comparison with SKF-525A and ketoconazole. Drug Metab Pharmacokinet. 2003;18(5):287-95. [PubMed:15618748]
Details
10. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Sakaeda T, Iwaki K, Kakumoto M, Nishikawa M, Niwa T, Jin JS, Nakamura T, Nishiguchi K, Okamura N, Okumura K: Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol. 2005 Jun;57(6):759-64. [PubMed:15969931]
  2. Elsherbiny ME, El-Kadi AO, Brocks DR: The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci. 2008;11(1):147-59. [PubMed:18445370]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  3. Flockhart Table - Indiana University [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  3. Flockhart Table - Indiana University [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 Da
References
  1. Denner K, Vogel R, Schmalix W, Doehmer J, Bernhardt R: Cloning and stable expression of the human mitochondrial cytochrome P45011B1 cDNA in V79 Chinese hamster cells and their application for testing of potential inhibitors. Pharmacogenetics. 1995 Apr;5(2):89-96. [PubMed:7663533]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Gene Name
CYP11A1
Uniprot ID
P05108
Uniprot Name
Cholesterol side-chain cleavage enzyme, mitochondrial
Molecular Weight
60101.87 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Retinoic acid binding
Specific Function
Plays a key role in retinoic acid metabolism. Acts on retinoids, including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA. Capable of both 4-hydroxylation and 18-hydroxylation. Responsi...
Gene Name
CYP26A1
Uniprot ID
O43174
Uniprot Name
Cytochrome P450 26A1
Molecular Weight
56198.11 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name
CYP51A1
Uniprot ID
Q16850
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
56805.26 Da
References
  1. Matsuura K, Yoshioka S, Tosha T, Hori H, Ishimori K, Kitagawa T, Morishima I, Kagawa N, Waterman MR: Structural diversities of active site in clinical azole-bound forms between sterol 14alpha-demethylases (CYP51s) from human and Mycobacterium tuberculosis. J Biol Chem. 2005 Mar 11;280(10):9088-96. doi: 10.1074/jbc.M413042200. Epub 2004 Dec 20. [PubMed:15611056]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Yong WP, Ramirez J, Innocenti F, Ratain MJ: Effects of ketoconazole on glucuronidation by UDP-glucuronosyltransferase enzymes. Clin Cancer Res. 2005 Sep 15;11(18):6699-704. doi: 10.1158/1078-0432.CCR-05-0703. [PubMed:16166450]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Yong WP, Ramirez J, Innocenti F, Ratain MJ: Effects of ketoconazole on glucuronidation by UDP-glucuronosyltransferase enzymes. Clin Cancer Res. 2005 Sep 15;11(18):6699-704. doi: 10.1158/1078-0432.CCR-05-0703. [PubMed:16166450]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Leukotriene-b4 20-monooxygenase activity
Specific Function
Catalyzes leukotriene B4 omega-hydroxylation and arachidonic acid omega-hydroxylation but with an activity much lower than that of CYP4F2. Catalyzes the hydroxylation of the antihistamine ebastine.
Gene Name
CYP4F12
Uniprot ID
Q9HCS2
Uniprot Name
Cytochrome P450 4F12
Molecular Weight
60269.165 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Not Available
Gene Name
CYP4F2
Uniprot ID
P78329
Uniprot Name
Phylloquinone omega-hydroxylase CYP4F2
Molecular Weight
59852.825 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  2. Wang MZ, Saulter JY, Usuki E, Cheung YL, Hall M, Bridges AS, Loewen G, Parkinson OT, Stephens CE, Allen JL, Zeldin DC, Boykin DW, Tidwell RR, Parkinson A, Paine MF, Hall JE: CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O-demethylation of the antiparasitic prodrug DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime]. Drug Metab Dispos. 2006 Dec;34(12):1985-94. doi: 10.1124/dmd.106.010587. Epub 2006 Sep 22. [PubMed:16997912]

Transporters

Details
1. Bile salt export pump
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [PubMed:12739759]
  2. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. [PubMed:10820137]
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514]
  3. Wang EJ, Lew K, Casciano CN, Clement RP, Johnson WW: Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother. 2002 Jan;46(1):160-5. [PubMed:11751127]
  4. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. [PubMed:11961113]
  5. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389]
  6. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103]
  7. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. [PubMed:12235267]
  8. Dahan A, Sabit H, Amidon GL: The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport. AAPS J. 2009 Jun;11(2):205-13. doi: 10.1208/s12248-009-9092-5. Epub 2009 Mar 25. [PubMed:19319690]
  9. Takano M, Hasegawa R, Fukuda T, Yumoto R, Nagai J, Murakami T: Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells. Eur J Pharmacol. 1998 Oct 9;358(3):289-94. [PubMed:9822896]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [PubMed:10421612]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Karlgren M, Ahlin G, Bergstrom CA, Svensson R, Palm J, Artursson P: In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions. Pharm Res. 2012 Feb;29(2):411-26. doi: 10.1007/s11095-011-0564-9. Epub 2011 Aug 23. [PubMed:21861202]

Drug created on June 13, 2005 07:24 / Updated on September 24, 2018 02:40