Identification

Name
Luliconazole
Accession Number
DB08933
Type
Small Molecule
Groups
Approved
Description

Luliconazole is a topical antifungal agent that acts by unknown mechanisms but is postulated to involve altering the synthesis of fungi cell membranes. It was approved by the FDA (USA) in November 2013 and is marketed under the brand name Luzu. Luliconazole is also approved in Japan.

Structure
Thumb
Synonyms
Not Available
External IDs
NND-502 / PR-2699
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LuliconazoleCream10 mg/1gTopicalOceanside Pharmaceuticals2018-06-15Not applicableUs
LuzuCream10 mg/1gTopicalValeant Pharmaceuticals North America2013-11-14Not applicableUs
International/Other Brands
Lulicon (Pola Pharma )
Categories
UNII
RE91AN4S8G
CAS number
187164-19-8
Weight
Average: 354.27
Monoisotopic: 352.961495
Chemical Formula
C14H9Cl2N3S2
InChI Key
YTAOBBFIOAEMLL-REQDGWNSSA-N
InChI
InChI=1S/C14H9Cl2N3S2/c15-9-1-2-10(11(16)5-9)13-7-20-14(21-13)12(6-17)19-4-3-18-8-19/h1-5,8,13H,7H2/b14-12+/t13-/m0/s1
IUPAC Name
2-[(2E,4R)-4-(2,4-dichlorophenyl)-1,3-dithiolan-2-ylidene]-2-(1H-imidazol-1-yl)acetonitrile
SMILES
ClC1=CC(Cl)=C(C=C1)[C@@H]1CS\C(S1)=C(\C#N)N1C=CN=C1

Pharmacology

Indication

Luliconazole is indicated in adults aged 18 years and older for the topical treatment of fungal infections caused by Trichophyton rubrum and Epidermophyton floccosum, specifically tinea pedis, cruris, and corporis.

Associated Conditions
Pharmacodynamics

Luliconazole kills the organisms Trichophyton rubrum and Epidermophyton floccosum, most likely by altering their fungal cell membranes.

Mechanism of action

The exact mechanism of action for luliconazole's anti-fungal activity is still not known, but luliconazole is thought to inhibit the enzyme lanosterol demethylase. Lanosterol demethylase is needed for the synthesis of ergosterol, which is a major component of the fungus cell membranes.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
inhibitor
Yeast
Absorption

Although luliconazole is administered topically, clinical studies have shown that after the first dose in patients with tina pedis, a maximum plasma concentration of 0.40 ± 0.76 ng/mL (mean ± SD) occurred in 16.9 ± 9.39 hours (mean ± SD).

Volume of distribution

The volume of distribution was not quantified.

Protein binding

Plasma protein binding of luliconazole is >99%.

Metabolism

The metabolism of luliconazole has yet to be determined.

Route of elimination

The route of elimination of luliconazole has yet to be determined.

Half life

The half life of luliconazole has yet to be determined.

Clearance

The clearance of luliconazole has yet to be determined.

Toxicity

In clinical trials, no serious toxicity was reported, only local irritation (mild contact dermatitis and cellulitis) at the site of application was found.

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

Interactions

Drug Interactions
DrugInteraction
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Luliconazole.
AbirateroneThe serum concentration of Abiraterone can be increased when it is combined with Luliconazole.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Luliconazole.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Luliconazole.
AdinazolamThe serum concentration of Adinazolam can be increased when it is combined with Luliconazole.
AgmatineThe serum concentration of Agmatine can be increased when it is combined with Luliconazole.
AlbendazoleThe serum concentration of Albendazole can be increased when it is combined with Luliconazole.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Luliconazole.
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Luliconazole.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Luliconazole.
Food Interactions
No interactions found.

References

Synthesis Reference

Niwano Y, Kuzuhara N, Kodama H, Yoshida M, Miyazaki T, Yamaguchi H: In vitro and in vivo antidermatophyte activities of NND-502, a novel optically active imidazole antimycotic agent. Antimicrob Agents Chemother. 1998 Apr;42(4):967-70.

General References
  1. Niwano Y, Kuzuhara N, Kodama H, Yoshida M, Miyazaki T, Yamaguchi H: In vitro and in vivo antidermatophyte activities of NND-502, a novel optically active imidazole antimycotic agent. Antimicrob Agents Chemother. 1998 Apr;42(4):967-70. [PubMed:9559824]
  2. Uchida K, Nishiyama Y, Yamaguchi H: In vitro antifungal activity of luliconazole (NND-502), a novel imidazole antifungal agent. J Infect Chemother. 2004 Aug;10(4):216-9. [PubMed:15365862]
External Links
KEGG Drug
D01980
KEGG Compound
C13478
PubChem Compound
3003141
PubChem Substance
175427163
ChemSpider
2273807
ChEBI
34825
ChEMBL
CHEMBL2105689
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Luliconazole
ATC Codes
D01AC18 — Luliconazole
FDA label
Download (199 KB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentOnychomycosis1
2, 3CompletedTreatmentDistal and Lateral Subungual Onychomycosis1
4CompletedTreatmentTinea Corporis1
4CompletedTreatmentTinea Cruris / Tinea Pedis1
4Not Yet RecruitingTreatmentTinea infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CreamTopical10 mg/1g
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5900488No1996-07-052016-07-05Us
US9012484No2013-09-062033-09-06Us
US8980931No2014-04-282034-04-28Us
US9199977No2013-09-062033-09-06Us
US9453006No2013-09-062033-09-06Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0659 mg/mLALOGPS
logP4.27ALOGPS
logP4.07ChemAxon
logS-3.7ALOGPS
pKa (Strongest Basic)6.34ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area41.61 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity101 m3·mol-1ChemAxon
Polarizability33.65 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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 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 / 1,3-dithiolanes / Nitriles / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
1,3-dichlorobenzene / Aryl chloride / Aryl halide / N-substituted imidazole / Azole / Heteroaromatic compound / Dithiolane / 1,3-dithiolane / Imidazole / Azacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
dichlorobenzene (CHEBI:34825)

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. Niwano Y, Koga H, Kodama H, Kanai K, Miyazaki T, Yamaguchi H: Inhibition of sterol 14 alpha-demethylation of Candida albicans with NND-502, a novel optically active imidazole antimycotic agent. Med Mycol. 1999 Oct;37(5):351-5. [PubMed:10520160]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
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. luliconazole - Drug Summary PDR [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
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. luliconazole - Drug Summary PDR [Link]
  2. Luliconazole FDA label [File]

Drug created on December 29, 2013 15:57 / Updated on September 13, 2018 15:57