Identification

Name
Clotrimazole
Accession Number
DB00257  (APRD00244)
Type
Small Molecule
Groups
Approved, Vet approved
Description

An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [PubChem]

Structure
Thumb
Synonyms
  • 1-((2-Chlorophenyl)diphenylmethyl)-1H-imidazole
  • 1-(alpha-(2-Chlorophenyl)benzhydryl)imidazole
  • 1-(O-Chloro-alpha,alpha-diphenylbenzyl)imidazole
  • 1-(o-Chloro-α,α-diphenylbenzyl)imidazole
  • 1-(o-Chlorotrityl)imidazole
  • 1-(α-(2-Chlorophenyl)benzhydryl)imidazole
  • Clotrimazole
  • Lotrimin (tn)
  • Mycelex (tn)
External IDs
BAY 5097 / BAY-5097
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LotriminCream10 mg/1gTopicalPhysicians Total Care, Inc.1994-11-282005-06-30Us
LotriminSolution10 mg/1mLTopicalPhysicians Total Care, Inc.2000-11-032005-06-30Us
MycelexTroche10 mg/1OralBayer Pharmaceuticals Corp2006-08-14Not applicableUs
MycelexTroche10 mg/1OralPhysicians Total Care, Inc.1983-06-172011-05-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ClotrimazoleCream10 mg/1gTopicalGlenmark Pharmaceuticals Inc.,Usa2010-08-04Not applicableUs
ClotrimazoleCream10 mg/1gTopicalE. Fougera & Co. a division of Fougera Pharmaceuticals Inc.2008-09-02Not applicableUs
ClotrimazoleLozenge10 mg/1OralPhysicians Total Care, Inc.2009-07-23Not applicableUs
ClotrimazoleLozenge10 mg/1Oral; TopicalCardinal Health2004-07-29Not applicableUs
ClotrimazoleCream10 mg/1gTopicalLake Erie Medical Dba Quality Care Produts Llc2010-08-04Not applicableUs
ClotrimazoleLozenge10 mg/1Oral; TopicalWest-Ward Pharmaceuticals Corp.2004-07-29Not applicableUs
ClotrimazoleSolution10 mg/1mLTopicalPhysicians Total Care, Inc.1996-07-292011-06-30Us
ClotrimazoleSolution10 mg/1mLTopicalTaro Pharmaceuticals U.S.A., Inc.1996-07-29Not applicableUs
ClotrimazoleLozenge10 mg/1OralRemedy Repack2012-07-202014-02-19Us
ClotrimazoleCream10 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.1993-08-31Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Akin Anti-FungalSolution10 mg/1mLTopicalSouthern Sales & Service, Inc.2017-01-01Not applicableUs
AlevazolOintment10 mg/1gTopicalCapital Pharmaceutical2014-09-01Not applicableUs
Anti FungalLiquid1 g/100mLTopicalGuangzhou Ertiantang Pharmaceutical Co.,ltd2017-09-22Not applicableUs
Anti-FungalCream10 mg/1gTopicalMPM Medical, Inc.2002-10-14Not applicableUs
AntifungalCream10 mg/1gTopicalRite Aid2011-04-15Not applicableUs
AntifungalCream1 g/100gTopicalSafeway2008-11-202017-04-14Us
AntifungalCream1 g/100gTopicalGalentic Pharma (India) Private Limited2013-08-07Not applicableUs
Antifungal FootCream1 g/100gTopicalHyvee2015-11-28Not applicableUs
Aptrimazole 1.0% Antifungal CreamCream1 g/100gTopicalA P J Laboratories Limited2013-04-27Not applicableUs
Aspiera Anti-FungalOintment1.0 g/100gTopicalAidance Skincare & Topical Solutions, LLC2012-05-31Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Betamethasone ClotrimazoleClotrimazole (10 mg/1) + Betamethasone dipropionate (0.64 mg/1)CreamTopicalStat Rx USA2002-08-02Not applicableUs
Canesoral Combi-pakClotrimazole (1 %) + Fluconazole (150 mg)Capsule; CreamOral; Topical; VaginalBayer2010-03-10Not applicableCanada
Canesten 1 Vaginal Tablet Combi-pakClotrimazole (1 %) + Clotrimazole (500 mg)Cream; SuppositoryTopical; VaginalBayer Inc Consumer Care1995-12-312007-08-02Canada
Canesten 1 Vaginal Tablet Combi-pakClotrimazole (1 %) + Clotrimazole (500 mg)Cream; SuppositoryTopical; VaginalBayer Inc Consumer Care1995-12-312007-08-02Canada
Canesten 3 Vaginal Tablet Combi-pakClotrimazole (1 %) + Clotrimazole (200 mg)Cream; SuppositoryTopical; VaginalBayer Inc Consumer Care1995-12-312007-08-02Canada
Canesten 3 Vaginal Tablet Combi-pakClotrimazole (1 %) + Clotrimazole (200 mg)Cream; SuppositoryTopical; VaginalBayer Inc Consumer Care1995-12-312007-08-02Canada
Canesten Combi-pak 1 Day TherapyClotrimazole (1 %) + Clotrimazole (500 mg)Cream; SuppositoryTopical; VaginalMiles Inc. Pharmaceutical Division1994-12-311996-09-09Canada
Canesten Combi-pak 1 Day TherapyClotrimazole (1 %) + Clotrimazole (500 mg)Cream; SuppositoryTopical; VaginalMiles Inc. Pharmaceutical Division1994-12-311996-09-09Canada
Canesten Combi-pak Comfortab 1Clotrimazole (1 %) + Clotrimazole (500 mg)Cream; TabletTopical; VaginalBayer2006-05-12Not applicableCanada
Canesten Combi-pak Comfortab 1Clotrimazole (1 %) + Clotrimazole (500 mg)Cream; TabletTopical; VaginalBayer2006-05-12Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Terbinafine HCl Chlortimazole and TolnaftateClotrimazole (1 g/100mL) + Terbinafine Hydrochloride (1 g/100mL) + Tolnaftate (1 g/100mL)SolutionTopicalDr Marc's Manufacturing And Sales2018-01-302018-04-18Us
International/Other Brands
Canesten (Bayer) / Canifug (Dr. August Wolff) / Clotrimaderm (Taro) / Empecid (Bayer) / FemCare / Fungicip (Cipla) / Gyne-Lotrimin (Schering-Plough) / Mycelex (Bayer) / Myclo-Derm / Myclo-Gyne
Categories
UNII
G07GZ97H65
CAS number
23593-75-1
Weight
Average: 344.837
Monoisotopic: 344.108026261
Chemical Formula
C22H17ClN2
InChI Key
VNFPBHJOKIVQEB-UHFFFAOYSA-N
InChI
InChI=1S/C22H17ClN2/c23-21-14-8-7-13-20(21)22(25-16-15-24-17-25,18-9-3-1-4-10-18)19-11-5-2-6-12-19/h1-17H
IUPAC Name
1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole
SMILES
ClC1=CC=CC=C1C(N1C=CN=C1)(C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

For the local treatment of oropharyngeal candidiasis and vaginal yeast infections, also used in fungal infections of the skin such as ringworm, athlete's foot, and jock itch.

Associated Conditions
Pharmacodynamics

Clotrimazole, an imidazole derivative with a broad spectrum of antimycotic activity, inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. Betamethasone and clotrimazole are used together to treat cutaneous tinea infections. In studies in fungal cultures, the minimum fungicidal concentration of clotrimazole caused leakage of intracellular phosphorous compounds into the ambient medium with concomitant breakdown of cellular nucleic acids, and accelerated potassium etflux. Both of these events began rapidly and extensively after addition of the drug to the cultures. The primary action of clotrimazole is against dividing and growing organisms.

Mechanism of action

Clotrimazole interacts with yeast 14-α demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the membrane. In this way, clotrimazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Clotrimazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
antagonist
inhibitor
Yeast
AIntermediate conductance calcium-activated potassium channel protein 4
inhibitor
Human
UNuclear receptor subfamily 1 group I member 2
activator
Human
UNuclear receptor subfamily 1 group I member 3
partial agonist
Human
Absorption

Poorly and erratically absorbed orally, minimal vaginal or topical absorption.

Volume of distribution
Not Available
Protein binding

90%

Metabolism

Hepatic (metabolized to inactive metabolites)

Route of elimination
Not Available
Half life

2 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps.

Affected organisms
  • Yeast and other fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Clotrimazole.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Clotrimazole.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Clotrimazole.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Clotrimazole.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Clotrimazole.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Clotrimazole.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Clotrimazole.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Clotrimazole.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Clotrimazole.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Clotrimazole.
Food Interactions
Not Available

References

Synthesis Reference

Buechel, K.H., et al; South African Patent 69/0039; January 3, 1969; assigned to Farben- Buechel, K.H., Regel, E. and Plempel, M.; US. Patent 3,660,577; May 2,1972; and U.S. fabriken Bayer AG, Germany. Patent 3,705,172; Dec. 5,1972; both assigned to Farbenfabriken Bayer A.G. (Germany).

US3705172
General References
Not Available
External Links
Human Metabolome Database
HMDB0001922
KEGG Drug
D00282
KEGG Compound
C06922
PubChem Compound
2812
PubChem Substance
46507927
ChemSpider
2710
BindingDB
31774
ChEBI
3764
ChEMBL
CHEMBL104
Therapeutic Targets Database
DAP000138
PharmGKB
PA449057
IUPHAR
2330
Guide to Pharmacology
GtP Drug Page
HET
CL6
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Clotrimazole
ATC Codes
D01AC01 — ClotrimazoleG01AF02 — ClotrimazoleG01AF20 — Combinations of imidazole derivativesA01AB18 — Clotrimazole
AHFS Codes
  • 84:04.08.08 — Azoles
PDB Entries
2xfh / 3mdv / 4xe3
FDA label
Download (139 KB)
MSDS
Download (73.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionHIV- Prevention1
1CompletedTreatmentAutoimmune Diseases / Disseminated or Multiple Sclerosis Nos / Disseminated Sclerosis / Multiple Sclerosis, Acute Relapsing / Multiple Sclerosis, Chronic Progressive / Multiple Sclerosis, Primary Progressive1
1, 2CompletedTreatmentKidney Diseases / Transplantation, Kidney1
1, 2CompletedTreatmentSickle Cell Disorders1
1, 2RecruitingTreatmentVulvovaginal Candidiasis1
1, 2SuspendedTreatmentIleitis / Inflammatory Bowel Diseases (IBD) / Pouchitis / Ulcerative Colitis (UC)1
2RecruitingTreatmentKeratotic Nodular Size1
2, 3Not Yet RecruitingTreatmentCandidiasis infection1
2, 3RecruitingTreatmentInfections, Fungal1
2, 3RecruitingTreatmentVulvovaginal Candidiasis (VVC)1
2, 3SuspendedTreatmentFolliculitis1
3CompletedPreventionCandidiasis infection / Human Immunodeficiency Virus (HIV) Infections / Mycoses1
3CompletedTreatmentClotrimazole / Ovulen / Vulvovaginal Candidiasis1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentOtomycosis1
3Unknown StatusTreatmentInfections, Fungal / Tinea Corporis / Tinea Cruris / Tinea Pedis1
3WithdrawnTreatmentSexual Active Women / Vaginal Discharge1
4CompletedHealth Services ResearchChronic Renal Failure (CRF)1
4RecruitingTreatmentBacterial Vaginosis (BV) / Candidiasis infection1
4TerminatedTreatmentAtopic Dermatitis (AD) / Skin Diseases, Eczematous1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Oral Candidiasis1
Not AvailableCompletedTreatmentOtomycosis1
Not AvailableCompletedTreatmentSickle Cell Disorders1
Not AvailableNo Longer AvailableNot AvailableDiabetes, Diabetes Mellitus Type 11
Not AvailableRecruitingNot AvailableVaginal Candida1

Pharmacoeconomics

Manufacturers
  • Schering plough healthcare products inc
  • Bayer pharmaceuticals corp
  • Glenmark pharmaceuticals inc usa
  • Nycomed us inc
  • Taro pharmaceuticals usa inc
  • Actavis mid atlantic llc
  • Taro pharmaceuticals inc
  • Schering corp sub schering plough corp
  • Teva pharmaceuticals usa inc
  • Bayer healthcare pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Paddock laboratories inc
  • Roxane laboratories inc
Packagers
  • Actavis Group
  • Alza Corp.
  • Bayer Healthcare
  • Bergen Brunswig
  • Cardinal Health
  • CVS Pharmacy
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • E. Fougera and Co.
  • H.J. Harkins Co. Inc.
  • Ivax Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • McNeil Laboratories
  • Medisca Inc.
  • Neuman Distributors Inc.
  • Novartis AG
  • Nycomed Inc.
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Paddock Labs
  • Palmetto Pharmaceuticals Inc.
  • PEDiNOL
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Resource Optimization and Innovation LLC
  • Rite Aid Corp.
  • Roxane Labs
  • S&P Healthcare
  • Sandhills Packaging Inc.
  • Schering Corp.
  • Schering-Plough Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • Walgreen Co.
  • Warrick Pharmaceuticals Corp.
Dosage forms
FormRouteStrength
OintmentTopical10 mg/1g
LiquidTopical1 g/100mL
CreamTopical350 mg/35g
LotionTopical1 g/100mL
Capsule; creamOral; Topical; Vaginal
SolutionTopical1 %
CreamTopical; Vaginal2 %
SuppositoryVaginal200 mg
Cream; suppositoryTopical; Vaginal
Cream; tabletTopical; Vaginal
CreamTopical; Vaginal
TabletVaginal500 mg
TabletVaginal200 mg
CreamVaginal10 %
CreamTopical1 %
CreamTopical; Vaginal1 %
LiquidTopical1 %
SuppositoryVaginal100 mg
CreamTopical1 g/1g
Capsule; cream; kitOral; Topical
CreamTopical1 g/100g
CreamTopical10 mg/1g
CreamTopical50 mg/1g
CreamVaginal1 g/100g
CreamVaginal10 mg/1g
LiquidTopical1 mg/1mL
LozengeOral10 mg/1
LozengeOral; Topical10 mg/1
SolutionTopical1 g/1mL
SolutionTopical10 mg/1mL
CreamVaginal1 %
CreamVaginal2 %
CreamVaginal2 g/100g
SolutionTopical1 mg/1mL
CreamTopical0.01 g/1g
Aerosol, sprayTopical1 mL/100mL
Aerosol, foamTopical1 g/100g
LiquidTopical10 g/1000g
SolutionTopical1 g/100mL
GelTopical10 mg/1g
LiquidTopical10 mg/1mL
SprayTopical4 mg/1mL
PowderTopical1.0 g/100g
CreamTopical6 mg/1mL
CreamTopical10 g/1g
OintmentTopical1 mg/100g
GelTopical1 g/100g
CreamTopical420 mg/42g
CreamTopical
LotionTopical
TrocheOral10 mg/1
CreamVaginal50 mg
LiquidTopical10 mg
CreamTopical10 mg
SolutionTopical10 mg
CreamTopical; Vaginal10 mg
Aerosol, foamTopical10 mg/1g
CreamTopical1.0 g/100g
OintmentTopical2.0 g/100g
OilTopical10 mg/1mL
CreamTopical10 mg/1mL
CreamTopical0.01 mg/10g
CreamTopical1.1 g/115g
SolutionTopical
OintmentTopical1.0 g/100g
Kit
CreamTopical10 mg/100g
Prices
Unit descriptionCostUnit
Clotrimazole 70 10 mg Troche Bottle117.04USD bottle
Clotrimazole 1% Cream 45 gm Tube49.99USD tube
Clotrimazole 1% Cream 30 gm Tube35.99USD tube
Clotrimazole 1% Solution 30ml Bottle24.99USD bottle
Clotrimazole 1% Cream 15 gm Tube17.99USD tube
Clotrimazole 1% Solution 10ml Bottle17.99USD bottle
Clotrimazole powder5.2USD g
Mycelex 10 mg troche1.85USD troche
Clotrimazole 10 mg troche1.61USD troche
Mycelex-7 100 mg vaginal tablet1.33USD tablet
Lotrimin 1% cream1.28USD g
Gyne-lotrimin insert1.03USD insert
Mycelex 1% cream0.9USD g
Clotrimazole insert0.86USD insert
Lotrimin ultra 1% cream0.68USD g
Clotrimazole 1% cream0.53USD g
Clotrimazole 3 2% cream0.5USD g
Ra clotrimazole 3 cream0.46USD g
Ra athlete's 1% foot cream0.37USD g
Desenex 1% cream0.33USD g
CVS Pharmacy clotrimazole 1% cream0.32USD g
Antifungal 1% cream0.27USD g
Sm antifungal 1% cream0.25USD g
Ra clotrimazole af cream0.24USD g
Clotrim 1% vaginal cream0.18USD g
Lotrimin af 2% spray powder0.05USD g
Lotrimin af 2% liquid spray0.04USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)154-156Buechel, K.H., et al; South African Patent 69/0039; January 3, 1969; assigned to Farben- Buechel, K.H., Regel, E. and Plempel, M.; US. Patent 3,660,577; May 2,1972; and U.S. fabriken Bayer AG, Germany. Patent 3,705,172; Dec. 5,1972; both assigned to Farbenfabriken Bayer A.G. (Germany).
water solubility29.84 mg/mLNot Available
logP6.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00147 mg/mLALOGPS
logP5.48ALOGPS
logP5.84ChemAxon
logS-5.4ALOGPS
pKa (Strongest Basic)6.62ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area17.82 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity103.76 m3·mol-1ChemAxon
Polarizability36.25 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9725
Blood Brain Barrier+0.9837
Caco-2 permeable+0.6858
P-glycoprotein substrateNon-substrate0.7185
P-glycoprotein inhibitor INon-inhibitor0.6612
P-glycoprotein inhibitor IINon-inhibitor0.7884
Renal organic cation transporterNon-inhibitor0.5854
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9149
CYP450 3A4 substrateNon-substrate0.6262
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.8478
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9799
Ames testNon AMES toxic0.7428
CarcinogenicityNon-carcinogens0.9018
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7194 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9659
hERG inhibition (predictor II)Inhibitor0.6779
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-004i-1490000000-442fa75d6a2d80321e36
MS/MS Spectrum - Quattro_QQQ 10V, N/ALC-MS/MSsplash10-004i-0090000000-9ac001e37a55e61bc916
MS/MS Spectrum - Quattro_QQQ 25V, N/ALC-MS/MSsplash10-004i-0290000000-6285150b307e50af52c7
MS/MS Spectrum - Quattro_QQQ 40V, N/ALC-MS/MSsplash10-016u-0690000000-5814802384fae84ca3df
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
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-23b69c41217f6b148307
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-016r-0960000000-5b3632c056ca1c0fa601
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-016r-0950000000-bcb189995c8cdcd62304
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-f1d5f44ac74388f9bf4f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-1490000000-1ed188e9911ad62a7fc7
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0390000000-c2f0490842646cf25d56
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014l-3970000000-0cf80068015e539b67c9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00or-0391000000-e8d9d4c77703a87fdcd8
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as triphenyl compounds. These are aromatic compounds containing a triphenyl moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Triphenyl compounds
Sub Class
Not Available
Direct Parent
Triphenyl compounds
Alternative Parents
Chlorobenzenes / N-substituted imidazoles / Aryl chlorides / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Triphenyl compound / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / N-substituted imidazole / Azole / Heteroaromatic compound / Imidazole
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
conazole antifungal drug, imidazoles, imidazole antifungal drug, monochlorobenzenes (CHEBI:3764) / a small molecule (CPD-8926)

Targets

Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Antagonist
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. 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]
  2. Gachotte D, Pierson CA, Lees ND, Barbuch R, Koegel C, Bard M: A yeast sterol auxotroph (erg25) is rescued by addition of azole antifungals and reduced levels of heme. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11173-8. [PubMed:9326581]
  3. Henry KW, Nickels JT, Edlind TD: Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother. 2000 Oct;44(10):2693-700. [PubMed:10991846]
  4. Lorenz RT, Parks LW: Physiological effects of fenpropimorph on wild-type Saccharomyces cerevisiae and fenpropimorph-resistant mutants. Antimicrob Agents Chemother. 1991 Aug;35(8):1532-7. [PubMed:1929324]
  5. 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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein phosphatase binding
Specific Function
Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Requi...
Gene Name
KCNN4
Uniprot ID
O15554
Uniprot Name
Intermediate conductance calcium-activated potassium channel protein 4
Molecular Weight
47695.12 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Brugnara C, Gee B, Armsby CC, Kurth S, Sakamoto M, Rifai N, Alper SL, Platt OS: Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. J Clin Invest. 1996 Mar 1;97(5):1227-34. [PubMed:8636434]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
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. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, Lindley C, Yan B, Negishi M, LeCluyse EL: Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos. 2004 Mar;32(3):348-58. [PubMed:14977870]
  2. Smith CM, Faucette SR, Wang H, LeCluyse EL: Modulation of UDP-glucuronosyltransferase 1A1 in primary human hepatocytes by prototypical inducers. J Biochem Mol Toxicol. 2005;19(2):96-108. [PubMed:15849716]
  3. 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]
  4. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
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. Kanno Y, Inouye Y: A consecutive three alanine residue insertion mutant of human CAR: a novel CAR ligand screening system in HepG2 cells. J Toxicol Sci. 2010 Aug;35(4):515-25. [PubMed:20686338]

Enzymes

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. 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]
Details
2. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
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. Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, Kumar G, McLeod J, Obach SR, Roberts S, Roe A, Shah A, Snikeris F, Sullivan JT, Tweedie D, Vega JM, Walsh J, Wrighton SA: The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharmacol. 2003 May;43(5):443-69. [PubMed:12751267]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Monostory K, Hazai E, Vereczkey L: Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors. Chem Biol Interact. 2004 Apr 15;147(3):331-40. doi: 10.1016/j.cbi.2004.03.003. [PubMed:15135088]
  4. 16, 29. (2008). In Stockley's Drug Interactions (8th ed., pp. 598, 1071-1072). RPS Publishing. [ISBN:085369754X]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
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. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [PubMed:17101742]
  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. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, Lindley C, Yan B, Negishi M, LeCluyse EL: Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos. 2004 Mar;32(3):348-58. [PubMed:14977870]
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. Mason JI, Murry BA, Olcott M, Sheets JJ: Imidazole antimycotics: inhibitors of steroid aromatase. Biochem Pharmacol. 1985 Apr 1;34(7):1087-92. [PubMed:3921030]
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. 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. 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 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. 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]
Details
7. 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. 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
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. 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
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. 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
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Monostory K, Hazai E, Vereczkey L: Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors. Chem Biol Interact. 2004 Apr 15;147(3):331-40. doi: 10.1016/j.cbi.2004.03.003. [PubMed:15135088]
  2. Tassaneeyakul W, Birkett DJ, Miners JO: Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents. Xenobiotica. 1998 Mar;28(3):293-301. [PubMed:9574817]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
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. Usui T, Saitoh Y, Komada F: Induction of CYP3As in HepG2 cells by several drugs. Association between induction of CYP3A4 and expression of glucocorticoid receptor. Biol Pharm Bull. 2003 Apr;26(4):510-7. [PubMed:12673034]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Organic anion transmembrane transporter activity
Specific Function
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
Molecular Weight
169341.14 Da
References
  1. Teng S, Jekerle V, Piquette-Miller M: Induction of ABCC3 (MRP3) by pregnane X receptor activators. Drug Metab Dispos. 2003 Nov;31(11):1296-9. [PubMed:14570758]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
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. Geick A, Eichelbaum M, Burk O: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem. 2001 May 4;276(18):14581-7. Epub 2001 Jan 31. [PubMed:11297522]
  2. Schuetz EG, Beck WT, Schuetz JD: Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol. 1996 Feb;49(2):311-8. [PubMed:8632764]
  3. 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]
  4. 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]
  5. Bain LJ, LeBlanc GA: Interaction of structurally diverse pesticides with the human MDR1 gene product P-glycoprotein. Toxicol Appl Pharmacol. 1996 Nov;141(1):288-98. [PubMed:8917702]
  6. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Kauffmann HM, Pfannschmidt S, Zoller H, Benz A, Vorderstemann B, Webster JI, Schrenk D: Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression. Toxicology. 2002 Feb 28;171(2-3):137-46. [PubMed:11836020]
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. 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]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:40