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targets (1) enzymes (3)
for drugs
Identification
Name Econazole
Accession Number DB01127 (APRD00943)
Type small molecule
Groups approved
Description

A broad spectrum antimycotic with some action against Gram positive bacteria. It is used topically in dermatomycoses also orally and parenterally. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Econazole Nitrate
  • Ecostatin
  • Ecostatin cream
  • Ecostatin Vaginal Ovules
  • Gyno-Pevaryl
  • Gyno-Pevaryl 150
  • Ifenec
  • Palavale
  • Pevaryl
  • Spectazole
  • Spectazole cream
Brand name mixtures Not Available
Categories
  • Antifungal Agents
CAS number 27220-47-9
Weight Average: 381.684
Monoisotopic: 380.024996233
Chemical Formula C18H15Cl3N2O
InChI Key InChIKey=LEZWWPYKPKIXLL-UHFFFAOYSA-N
InChI
InChI=1S/C18H15Cl3N2O/c19-14-3-1-13(2-4-14)11-24-18(10-23-8-7-22-12-23)16-6-5-15(20)9-17(16)21/h1-9,12,18H,10-11H2
Plain Text
IUPAC Name
1-{2-[(4-chlorophenyl)methoxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole
SMILES
ClC1=CC=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzyl Alcohols and Derivatives
  • Phenethylamines
Substructures
  • Benzyl Alcohols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Imidazoles
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
Pharmacology
Indication For topical application in the treatment of tinea pedis, tinea cruris, and tinea corporis caused by Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Microsporum canis, Microsporum audouini, Microsporum gypseum, and Epidermophyton floccosum, in the treatment of cutaneous candidiasis, and in the treatment of tinea versicolor.
Pharmacodynamics Econazole is an antifungal medication related to fluconazole (Diflucan), ketoconazole (Nizoral), itraconazole (Sporanox), and clotrimazole (Lotrimin, Mycelex). Econazole prevents fungal organisms from producing vital substances required for growth and function. This medication is effective only for infections caused by fungal organisms. It will not work for bacterial or viral infections.
Mechanism of action Econazole 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. Econazole 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.
Absorption After topical application to the skin of normal subjects, systemic absorption of econazole nitrate is extremely low. Although most of the applied drug remains on the skin surface, drug concentrations were found in the stratum corneum which, by far, exceeded the minimum inhibitory concentration for dermatophytes.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic.
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Overdosage of econazole in humans has not been reported to date. In mice, rats guinea pigs and dogs, the oral LD 50 values were found to be 462, 668, 272, and > 160 mg/kg, respectively.
Affected organisms
  • Yeast and other fungi
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Altana inc
  • Perrigo new york inc
  • Prasco llc dba prasco laboratories
  • Taro pharmaceuticals usa inc
  • Orthoneutrogena
Packagers
Dosage forms
Form Route Strength
Suppository Intravaginal
Prices
Unit description Cost Unit
Econazole Nitrate 1% Cream 85 gm Tube 73.63 USD tube
Econazole Nitrate 1% Cream 30 gm Tube 32.16 USD tube
Econazole Nitrate 1% Cream 15 gm Tube 19.32 USD tube
Econazole nitrate powder 2.5 USD g
Spectazole 1% cream 1.33 USD g
Econazole nitrate 1% cream 0.93 USD g
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 5.5 PhysProp
Predicted Properties
Property Value Source
water solubility 1.48e-03 g/l ALOGPS
logP 4.67 ALOGPS
logP 5.35 ChemAxon Molconvert
logS -5.41 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 27.05 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 98.26 ChemAxon Molconvert
polarizability 37.37 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D03936 Link_out
KEGG Compound C08068 Link_out
PubChem Compound 3198 Link_out
PubChem Substance 46508881 Link_out
ChemSpider 3086 Link_out
ChEBI 4754 Link_out
ChEMBL 4754 Link_out
Therapeutic Targets Database DAP001269 Link_out
PharmGKB PA449430 Link_out
Drug Product Database 2011948 Link_out
RxList http://www.rxlist.com/cgi/generic3/econazole.htm Link_out
Drugs.com http://www.drugs.com/cdi/econazole-cream.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/spe1410.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Econazole Link_out
ATC Codes
  • D01AC03
  • G01AF05
AHFS Codes
  • 84:04.08.08
PDB Entries Not Available
FDA label show (202.5 KB)
MSDS show (72.9 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Cytochrome P450 51

Pharmacological action: yes
Actions: antagonist

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

Organism class: fungal
UniProt ID: P10613 Link_out
Gene: ERG11
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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 Jul 12. Pubmed
  3. Strushkevich N, Usanov SA, Park HW: Structural basis of human CYP51 inhibition by antifungal azoles. J Mol Biol. 2010 Apr 9;397(4):1067-78. Epub 2010 Feb 10. Pubmed
  4. Jackson CJ, Lamb DC, Kelly DE, Kelly SL: Bactericidal and inhibitory effects of azole antifungal compounds on Mycobacterium smegmatis. FEMS Microbiol Lett. 2000 Nov 15;192(2):159-62. Pubmed
  5. Pietila MP, Vohra PK, Sanyal B, Wengenack NL, Raghavakaimal S, Thomas CF Jr: Cloning and characterization of CYP51 from Mycobacterium avium. Am J Respir Cell Mol Biol. 2006 Aug;35(2):236-42. Epub 2006 Mar 16. Pubmed
  6. 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
Enzymes

1. Cytochrome P450 19A1

Actions: inhibitor

Catalyzes the formation of aromatic C18 estrogens from C19 androgens

UniProt ID: P11511 Link_out
Gene: CYP19A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2E1

Actions: inhibitor

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 or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Actions: inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on August 07, 2011 08:56

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.