Identification

Name
Sertaconazole
Accession Number
DB01153  (APRD00305)
Type
Small Molecule
Groups
Approved, Investigational
Description

Sertaconazole nitrate is an antifungal medication of the imidazole class. It is available as a cream to treat skin infections such as athlete's foot. [Wikipedia]

Structure
Thumb
Synonyms
  • Demofix
  • Sertaconazol
  • Sertaconazole
  • Sertaconazolum
Product Ingredients
IngredientUNIICASInChI Key
Sertaconazole nitrate1DV05410M599592-39-9HAAITRDZHUANGT-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ErtaczoCream20 mg/gTopicalValeant Pharmaceuticals North America2003-12-10Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ErtaczoCream20 mg/gTopicalRebel Distributors2003-12-10Not applicableUs
International/Other Brands
Ertaczo
Categories
UNII
72W71I16EG
CAS number
99592-32-2
Weight
Average: 437.77
Monoisotopic: 435.997066923
Chemical Formula
C20H15Cl3N2OS
InChI Key
JLGKQTAYUIMGRK-UHFFFAOYSA-N
InChI
InChI=1S/C20H15Cl3N2OS/c21-14-4-5-16(18(23)8-14)19(9-25-7-6-24-12-25)26-10-13-11-27-20-15(13)2-1-3-17(20)22/h1-8,11-12,19H,9-10H2
IUPAC Name
1-{2-[(7-chloro-1-benzothiophen-3-yl)methoxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole
SMILES
ClC1=CC(Cl)=C(C=C1)C(CN1C=CN=C1)OCC1=CSC2=C1C=CC=C2Cl

Pharmacology

Indication

For the topical treatment of interdigital tinea pedis in immunocompetent patients 12 years of age and older, caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

Associated Conditions
Pharmacodynamics

Sertaconazole is an imidazole/triazole type antifungal agent. Sertaconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Sertaconazole exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans.

Mechanism of action

Sertaconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Sertaconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
inhibitor
Yeast
Absorption

Bioavailability is negligible.

Volume of distribution
Not Available
Protein binding

>99% to plasma

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Yeast and other fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AgmatineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Agmatine.Experimental, Investigational
AmiodaroneThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Amiodarone.Approved, Investigational
AmlodipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Amlodipine.Approved
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Sertaconazole.Approved, Investigational
AmrinoneThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Amrinone.Approved
AranidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Aranidipine.Approved, Investigational
AtorvastatinThe risk or severity of myopathy can be increased when Sertaconazole is combined with Atorvastatin.Approved
AzelnidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Azelnidipine.Approved, Investigational
AzimilideThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Azimilide.Investigational
BarnidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Barnidipine.Approved
BencyclaneThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Bencyclane.Experimental
BenidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Benidipine.Approved, Investigational
BepridilThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Bepridil.Approved, Withdrawn
BioallethrinThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Bioallethrin.Approved, Experimental
BuspironeThe metabolism of Buspirone can be decreased when combined with Sertaconazole.Approved, Investigational
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Sertaconazole.Approved, Investigational
CarboxyamidotriazoleThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Carboxyamidotriazole.Investigational
CaroverineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Caroverine.Experimental
CilnidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Cilnidipine.Approved, Investigational
CinnarizineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Cinnarizine.Approved, Investigational
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Sertaconazole.Approved, Investigational, Withdrawn
ClevidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Clevidipine.Approved, Investigational
CyclandelateThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Cyclandelate.Approved
DarodipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Darodipine.Experimental
DexniguldipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Dexniguldipine.Experimental
DexverapamilThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Dexverapamil.Experimental
DidanosineDidanosine can cause a decrease in the absorption of Sertaconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
DiltiazemThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Diltiazem.Approved, Investigational
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Sertaconazole.Approved, Investigational
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Sertaconazole.Approved, Investigational
DotarizineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Dotarizine.Investigational
EfonidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Efonidipine.Approved, Investigational
EmopamilThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Emopamil.Experimental
EperisoneThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Eperisone.Approved, Investigational
EthosuximideThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Ethosuximide.Approved
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Sertaconazole.Approved
FelodipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Felodipine.Approved, Investigational
FendilineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Fendiline.Withdrawn
Fish oilThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Fish oil.Approved, Nutraceutical
FlunarizineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Flunarizine.Approved
FluspirileneThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Fluspirilene.Approved, Investigational
FosphenytoinThe serum concentration of Sertaconazole can be decreased when it is combined with Fosphenytoin.Approved, Investigational
GabapentinThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Gabapentin.Approved, Investigational
GallopamilThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Gallopamil.Investigational
IsradipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Isradipine.Approved, Investigational
LacidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Lacidipine.Approved, Investigational
LamotrigineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Lamotrigine.Approved, Investigational
LercanidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Lercanidipine.Approved, Investigational
LevetiracetamThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Levetiracetam.Approved, Investigational
LidoflazineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Lidoflazine.Experimental
LomerizineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Lomerizine.Experimental
LoperamideThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Loperamide.Approved
Magnesium sulfateThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Magnesium sulfate.Approved, Investigational, Vet Approved
ManidipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Manidipine.Approved, Investigational
MentholThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Menthol.Approved
MethsuximideThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Methsuximide.Approved
MibefradilThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Mibefradil.Investigational, Withdrawn
NaftopidilThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Naftopidil.Investigational
NicardipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Nicardipine.Approved, Investigational
NifedipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Nifedipine.Approved
NiguldipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Niguldipine.Experimental
NiludipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Niludipine.Experimental
NilvadipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Nilvadipine.Approved, Investigational
NimesulideThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Nimodipine.Approved, Investigational
NisoldipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Nisoldipine.Approved
NitrendipineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Nitrendipine.Approved, Investigational
NylidrinThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Nylidrin.Approved
OtiloniumThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Otilonium.Experimental, Investigational
PenfluridolThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Penfluridol.Experimental
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Sertaconazole.Approved, Vet Approved
PinaveriumThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Pinaverium.Approved
PrenylamineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Prenylamine.Withdrawn
ProgesteroneThe absorption of Progesterone can be decreased when combined with Sertaconazole.Approved, Vet Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Sertaconazole.Approved, Investigational
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Sertaconazole.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Sertaconazole.Approved, Investigational
RifapentineThe serum concentration of Rifapentine can be increased when it is combined with Sertaconazole.Approved, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Sertaconazole.Approved, Investigational
SeletracetamThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Seletracetam.Investigational
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Sertaconazole.Approved
SucralfateSucralfate can cause a decrease in the absorption of Sertaconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
SunitinibThe metabolism of Sunitinib can be decreased when combined with Sertaconazole.Approved, Investigational
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Sertaconazole.Approved, Investigational
TerodilineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Terodiline.Experimental
TetrahydropalmatineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Tetrahydropalmatine.Investigational
TetrandrineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Tetrandrine.Experimental
Tolfenamic AcidThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Tolfenamic Acid.Approved, Investigational
TranilastThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Tranilast.Approved, Investigational
TrimebutineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Trimebutine.Approved
TrimethadioneThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Trimethadione.Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Sertaconazole.Approved
VerapamilThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Verapamil.Approved
VinpocetineThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Vinpocetine.Investigational
WIN 55212-2The therapeutic efficacy of Sertaconazole can be increased when used in combination with WIN 55212-2.Experimental
ZiconotideThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Ziconotide.Approved
ZonisamideThe therapeutic efficacy of Sertaconazole can be increased when used in combination with Zonisamide.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015284
PubChem Compound
65863
PubChem Substance
46507290
ChemSpider
59273
ChEBI
83682
ChEMBL
CHEMBL1201196
Therapeutic Targets Database
DAP001270
PharmGKB
PA164748328
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sertaconazole
ATC Codes
D01AC14 — SertaconazoleG01AF20 — Combinations of imidazole derivativesG01AF19 — Sertaconazole
FDA label
Download (895 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentSkin Alterations Associated With Atopic Dermatitis1
3Unknown StatusTreatmentFoot Fungus / Ringworm / Tinea Pedis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
Dosage forms
FormRouteStrength
CreamTopical20 mg/g
Prices
Unit descriptionCostUnit
Ertaczo 2% Cream 30 gm Tube89.28USD tube
Ertaczo 2% cream2.6USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5135943No1994-05-312014-05-31Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleNot Available
logP6.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00637 mg/mLALOGPS
logP5.74ALOGPS
logP6.23ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)6.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area27.05 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity111.6 m3·mol-1ChemAxon
Polarizability42.93 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9879
Blood Brain Barrier+0.9837
Caco-2 permeable+0.5575
P-glycoprotein substrateSubstrate0.5548
P-glycoprotein inhibitor INon-inhibitor0.6546
P-glycoprotein inhibitor IIInhibitor0.91
Renal organic cation transporterInhibitor0.6041
CYP450 2C9 substrateNon-substrate0.8023
CYP450 2D6 substrateNon-substrate0.8745
CYP450 3A4 substrateNon-substrate0.6578
CYP450 1A2 substrateInhibitor0.9447
CYP450 2C9 inhibitorInhibitor0.9103
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorInhibitor0.9474
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9966
Ames testNon AMES toxic0.7933
CarcinogenicityNon-carcinogens0.8668
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.4642 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6979
hERG inhibition (predictor II)Inhibitor0.842
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
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 1-benzothiophenes. These are aromatic heterocyclic compound containing the Benzo[b]thiophene ring system.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiophenes
Sub Class
1-benzothiophenes
Direct Parent
1-benzothiophenes
Alternative Parents
Benzylethers / Dichlorobenzenes / N-substituted imidazoles / Aryl chlorides / Thiophenes / Heteroaromatic compounds / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 2 more
Substituents
1-benzothiophene / Benzylether / 1,3-dichlorobenzene / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / N-substituted imidazole
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
imidazoles, 1-benzothiophenes, ether, dichlorobenzene (CHEBI:83682)

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]

Enzymes

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. 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]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 07:53