Identification

Name
Oxiconazole
Accession Number
DB00239  (APRD01154)
Type
Small Molecule
Groups
Approved
Description

Oxiconazole nitrate (U.S.: Oxistat, Canada: Oxizole) is an antifungal medication typically administered in a cream or lotion to treat skin infections such as athlete's foot, jock itch and ringworm. [Wikipedia]

Structure
Thumb
Synonyms
  • Oxiconazol
  • Oxiconazole
  • Oxiconazolum
External IDs
Ro 13-8996
Product Ingredients
IngredientUNIICASInChI Key
Oxiconazole nitrateRQ8UL4C17S64211-46-7WVNOAGNOIPTWPT-NDUABGMUSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OxistatCream10 mg/1gTopicalPharma Derm, A Division Of Fougera Pharmaceuticals Inc.2006-01-252012-10-25Us
OxistatLotion30 mg/1gTopicalRebel Distributors2006-01-25Not applicableUs
OxistatCream10 mg/1gTopicalPharma Derm, A Division Of Fougera Pharmaceuticals Inc.1988-12-30Not applicableUs
OxistatCream10 mg/1gTopicalGlaxosmithkline Inc2006-02-022011-12-31Us
OxistatLotion10 mg/1gTopicalPharma Derm, A Division Of Fougera Pharmaceuticals Inc.2006-01-252012-12-04Us
OxistatLotion10 mg/1mLTopicalGlaxosmithkline Inc2006-02-022011-02-11Us
OxistatLotion10 mg/1mLTopicalPharma Derm, A Division Of Fougera Pharmaceuticals Inc.1992-09-30Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Oxiconazole NitrateCream10 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.2016-03-07Not applicableUs
Oxiconazole NitrateCream10 mg/1gTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.2016-03-09Not applicableUs
Oxiconazole Nitrate Cream 1%Cream10 mg/1gTopicalWelgo, Llc2016-08-012018-09-20Us
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OxizoleCream1 %TopicalValeo Pharma Corp.1998-05-212006-07-31Canada
OxizoleLotion10 mgTopicalStiefel Laboratories, Inc.1998-05-212002-04-02Canada
Categories
UNII
C668Q9I33J
CAS number
64211-45-6
Weight
Average: 429.12
Monoisotopic: 426.9812729
Chemical Formula
C18H13Cl4N3O
InChI Key
QRJJEGAJXVEBNE-HKOYGPOVSA-N
InChI
InChI=1S/C18H13Cl4N3O/c19-13-2-1-12(16(21)7-13)10-26-24-18(9-25-6-5-23-11-25)15-4-3-14(20)8-17(15)22/h1-8,11H,9-10H2/b24-18+
IUPAC Name
(Z)-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethylidene][(2,4-dichlorophenyl)methoxy]amine
SMILES
ClC1=CC(Cl)=C(CO\N=C(/CN2C=CN=C2)C2=CC=C(Cl)C=C2Cl)C=C1

Pharmacology

Indication

For treatment of dermal fungal infection.

Associated Conditions
Pharmacodynamics

Oxiconazole is a broad-spectrum imidazole derivative whose antifungal activity is derived primarily from the inhibition of ergosterol biosynthesis, which is critical for cellular membrane integrity. It has fungicidal or fungistatic activity in vitro against a number of pathogenic fungi including the following dermatophytes, and yeasts: T. rubrum, T. mentagrophytes, T. tonsurans, T. violaceum, E. floccosum, M. canis, M. audouini, M. gypseum, C. albicans, and M. furfur.

Mechanism of action

Oxiconazole inhibits ergosterol biosynthesis, which is required for cytoplasmic membrane integrity of fungi. It acts to destabilize the fungal cyctochrome P450 51 enzyme (also known as Lanosterol 14-alpha demethylase). This is vital in the cell membrance structure of the fungus. Its inhibition leads to cell lysis. Oxiconazole has also been shown in inhibit DNA synthesis and suppress intracellular concentrations of ATP. Like other imidazole antifungals, Oxiconazole can increase membrane permeability to zinc, augmenting its cytotoxicity.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
inhibitor
Yeast
ALanosterol synthase
inhibitor
Yeast
UNuclear receptor subfamily 1 group I member 2
partial agonist
Human
Absorption

Systemic absorption of oxiconazole is low.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Side effects incliude pruritus, burning, irritation, erythema, stinging and allergic contact dermatitis and folliculitis, fissuring, maceration rash and nodules.

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

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference
US4124767
General References
  1. Matsui H, Sakanashi Y, Oyama TM, Oyama Y, Yokota S, Ishida S, Okano Y, Oyama TB, Nishimura Y: Imidazole antifungals, but not triazole antifungals, increase membrane Zn2+ permeability in rat thymocytes Possible contribution to their cytotoxicity. Toxicology. 2008 Jun 27;248(2-3):142-50. doi: 10.1016/j.tox.2008.03.022. Epub 2008 Apr 7. [PubMed:18468760]
  2. Fromtling RA: Overview of medically important antifungal azole derivatives. Clin Microbiol Rev. 1988 Apr;1(2):187-217. [PubMed:3069196]
External Links
KEGG Drug
D08313
KEGG Compound
C08074
PubChem Compound
5353853
PubChem Substance
46504752
ChemSpider
4510239
BindingDB
50051844
ChEBI
7825
ChEMBL
CHEMBL1262
Therapeutic Targets Database
DAP001204
PharmGKB
PA164754742
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Oxiconazole
ATC Codes
D01AC11 — OxiconazoleG01AF17 — OxiconazoleG01AF20 — Combinations of imidazole derivatives
FDA label
Download (33.7 KB)
MSDS
Download (24.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentTinea Pedis1

Pharmacoeconomics

Manufacturers
  • Altana inc
Packagers
  • Dispensing Solutions
  • GlaxoSmithKline Inc.
  • Nycomed Inc.
  • Pharmaderm
  • Rebel Distributors Corp.
Dosage forms
FormRouteStrength
CreamTopical10 mg/1g
LotionTopical10 mg/1g
LotionTopical10 mg/1mL
LotionTopical30 mg/1g
CreamTopical1 %
LotionTopical10 mg
Prices
Unit descriptionCostUnit
Oxistat 1% Cream 60 gm Tube157.99USD tube
Oxistat 1% Lotion 30ml Bottle93.13USD bottle
Oxistat 1% Cream 30 gm Tube90.31USD tube
Oxistat 1% Cream 15 gm Tube48.99USD tube
Oxistat 1% cream2.23USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00191 mg/mLALOGPS
logP5.28ALOGPS
logP5.84ChemAxon
logS-5.4ALOGPS
pKa (Strongest Basic)6.74ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area39.41 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity105.95 m3·mol-1ChemAxon
Polarizability40.79 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9903
Blood Brain Barrier+0.9699
Caco-2 permeable+0.5346
P-glycoprotein substrateNon-substrate0.6346
P-glycoprotein inhibitor INon-inhibitor0.7469
P-glycoprotein inhibitor IIInhibitor0.8492
Renal organic cation transporterInhibitor0.8361
CYP450 2C9 substrateNon-substrate0.8221
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6122
CYP450 1A2 substrateInhibitor0.793
CYP450 2C9 inhibitorInhibitor0.6532
CYP450 2D6 inhibitorNon-inhibitor0.6844
CYP450 2C19 inhibitorInhibitor0.8635
CYP450 3A4 inhibitorInhibitor0.6477
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8414
Ames testNon AMES toxic0.7381
CarcinogenicityNon-carcinogens0.7601
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5642 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6542
hERG inhibition (predictor II)Inhibitor0.507
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 dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Dichlorobenzenes
Alternative Parents
N-substituted imidazoles / Aryl chlorides / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
1,3-dichlorobenzene / Aryl chloride / Aryl halide / N-substituted imidazole / Azole / Imidazole / Heteroaromatic compound / Organoheterocyclic compound / Azacycle / Organooxygen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
conazole antifungal drug, imidazoles, imidazole antifungal drug, oxime O-ether, dichlorobenzene (CHEBI:7825)

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. Carrillo-Munoz AJ, Giusiano G, Ezkurra PA, Quindos G: Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9. [PubMed:16964330]
  2. Rossello A, Bertini S, Lapucci A, Macchia M, Martinelli A, Rapposelli S, Herreros E, Macchia B: Synthesis, antifungal activity, and molecular modeling studies of new inverted oxime ethers of oxiconazole. J Med Chem. 2002 Oct 24;45(22):4903-12. [PubMed:12383016]
Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Inhibitor
General Function
Lanosterol synthase activity
Specific Function
Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus.
Gene Name
ERG7
Uniprot ID
Q04782
Uniprot Name
Lanosterol synthase
Molecular Weight
83713.975 Da
References
  1. Gebre-Hiwot A, Frommel D: The in-vitro anti-leishmanial activity of inhibitors of ergosterol biosynthesis. J Antimicrob Chemother. 1993 Dec;32(6):837-42. [PubMed:8144423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Mahajan MK, Uttamsingh V, Daniels JS, Gan LS, LeDuc BW, Williams DA: In vitro metabolism of oxymetazoline: evidence for bioactivation to a reactive metabolite. Drug Metab Dispos. 2011 Apr;39(4):693-702. doi: 10.1124/dmd.110.036004. Epub 2010 Dec 21. [PubMed:21177487]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:43