CICLOPIROX

First approved in 1982

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H17NO2
Molecular Weight	207.2689
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC(=O)N(O)C(=C1)C2CCCCC2

InChI

InChIKey=SCKYRAXSEDYPSA-UHFFFAOYSA-N

InChI=1S/C12H17NO2/c1-9-7-11(13(15)12(14)8-9)10-5-3-2-4-6-10/h7-8,10,15H,2-6H2,1H3

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021159s020lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21022s004lbl.pdf

Ciclopirox is an antifungal medication indicated for the treatment of seborrheic dermatitis (Loprox trade name) and onychomycosis of fingernails and toenails due to Trichophyton rubrum (Penlac trade name). The drug exerts its action by chelating Fe3+ and Al3+, resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Aluminium 2 Target ID: CHEMBL2366381 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021159s020lbl.pdf	Chelating Agent 142
Iron 18 Target ID: CHEMBL2363058 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021159s020lbl.pdf	Chelating Agent 142

Conditions

Condition	Modality	Targets	Highest Phase	Product
Seborrheic dermatitis 15 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021159s020lbl.pdf	Curative		Approved 8429	LOPROX Approved Use Loprox Shampoo is an antifungal indicated for the topical treatment of seborrheic dermatitis of the scalp in adults. Launch Date 1982
Onychomycosis of fingernails and toenails due to Trichophyton rubrum 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21022s004lbl.pdf	Curative		Approved 8429	PENALC Approved Use PENLAC NAIL LACQUER (ciclopirox) Topical Solution, 8%, as a component of a comprehensive management program, is indicated as topical treatment in immunocompetent patients with mild to moderate onychomycosis of fingernails and toenails without lunula involvement, due to Trichophyton rubrum. Launch Date 1999

C_max

Value	Dose	Co-administered	Analyte	Population
25.02 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/20519slr005_loprox_lbl.pdf	5 g single, topical dose: 5 g route of administration: Topical experiment type: SINGLE co-administered:		CICLOPIROX blood	Homo sapiens population: HEALTHY age: UNKNOWN sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/018748s024,019824s023,020519s016lbl.pdf	9 mg single, topical dose: 9 mg route of administration: Topical experiment type: SINGLE co-administered:		CICLOPIROX unknown	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
8 % 1 times / day multiple, topical Recommended Dose: 8 %, 1 times / day Route: topical Route: multiple Dose: 8 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21022s004lbl.pdf Page: p.11	unhealthy n = 281 Health Status: unhealthy Condition: Onychomycosis Population Size: 281 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21022s004lbl.pdf Page: p.11	Disc. AE: Creatine phosphokinase increased... AEs leading to discontinuation/dose reduction: Creatine phosphokinase increased (0.36%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21022s004lbl.pdf Page: p.11

AEs

AE	Significance	Dose	Population
Creatine phosphokinase increased	0.36% Disc. AE	8 % 1 times / day multiple, topical Recommended Dose: 8 %, 1 times / day Route: topical Route: multiple Dose: 8 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21022s004lbl.pdf Page: p.11	unhealthy n = 281 Health Status: unhealthy Condition: Onychomycosis Population Size: 281 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21022s004lbl.pdf Page: p.11

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			binder 2 activator 14 inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MATE1 306

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23241029/	no [IC50 >500 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	activator 14 Sources: https://pubmed.ncbi.nlm.nih.gov/21158687/
hERG 1647	binder 5 Sources: https://pubmed.ncbi.nlm.nih.gov/21158687/
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/21158687/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:453011	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:453011
ChemicalBook	CB7673863	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7673863
MolPort	MolPort-003-845-943	https://www.molport.com/shop/molecule-link/MolPort-003-845-943
Selleck Chemicals	Ciclopirox-Penlac	http://www.selleckchem.com/products/Ciclopirox-Penlac.html
ZINC	ZINC000000001145	http://zinc15.docking.org/substances/ZINC000000001145
eMolecules	901641	https://www.emolecules.com/cgi-bin/more?vid=901641

PubMed

Title	Date	PubMed
Successful treatment of dandruff with 1.5% ciclopirox olamine shampoo in Korea.	2003 Dec	14660265
Action mechanisms of modern antifungal agents and resulting problems in the management of onychomycosis.	2003 Dec	14641625
Polarographic determination of ciclopirox olamine in pure substance and in different pharmaceutical preparations.	2003 Dec	14630245
The use of topical therapies to treat onychomycosis.	2003 Jul	12956200
I've heard there's a nail polish for nail fungus. Does it work?	2003 Oct	14528182
Deep mycosis caused by Trichophyton mentagrophytes in a diabetic patient.	2003 Sep	12950910
A randomized comparison of nail surface remanence of three nail lacquers, containing amorolfine 5%, ciclopirox 8% or tioconazole 28%, in healthy volunteers.	2004	15573688
Assessing treatment outcomes in toenail onychomycosis clinical trials.	2004	15186193
Common fungal infections of the feet in patients with diabetes mellitus.	2004	14960127
Evaluation of the drug treatment and persistence of onychomycosis.	2004 Aug 31	15349516
Ciclopirox (Loprox) gel for superficial fungal infections.	2004 Aug-Sep	15334276
[Onychomycosis].	2004 Feb	14968324
Managing simple chronic paronychia and onycholysis with ciclopirox 0.77% and an irritant-avoidance regimen.	2004 Jan	14964637
Treatment of onychomycosis: pros and cons of antifungal agents.	2004 Jan-Feb	15688097
Onychomycosis in children: a brief overview with treatment strategies.	2004 Jan-Feb	14871333
Onychomycosis: review of recurrence rates, poor prognostic factors, and strategies to prevent disease recurrence.	2004 Jul	15287395
Management of onychomycosis: examining the role of monotherapy and dual, triple, or quadruple therapies.	2004 Jul	15287394
Safety and efficacy of ciclopirox 1% shampoo for the treatment of seborrheic dermatitis of the scalp in the US population: results of a double-blind, vehicle-controlled trial.	2004 Jul	15271196
Rationale of frequency of use of ciclopirox 1% shampoo in the treatment of seborrheic dermatitis: results of a double-blind, placebo-controlled study comparing the efficacy of once, twice, and three times weekly usage.	2004 Jul	15271195
Efficacy of different concentrations of ciclopirox shampoo for the treatment of seborrheic dermatitis of the scalp: results of a randomized, double-blind, vehicle-controlled trial.	2004 Jul	15271194
Ciclopirox: a broad-spectrum antifungal with antibacterial and anti-inflammatory properties.	2004 Jul	15271193
Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker for aberrant proliferation in intraepithelial neoplasia of the vulva.	2004 Jul	15262146
Tinea capitis favosa in Poland.	2004 Jun	15189196
Agar sublimation test for the in vitro determination of the antifungal activity of morpholine derivatives.	2004 Jun	15189181
Activation of HIF-1alpha mRNA by hypoxia and iron chelator in isolated rat carotid body.	2004 Jun 17	15182949
Ciclopirox shampoo for treating seborrheic dermatitis.	2004 Jun-Jul	15334279
The use of 40% urea cream in the treatment of moccasin tinea pedis.	2004 May	15186053
Cutaneous adiaspiromycosis: a distinct dermatologic entity associated with Chrysosporium species.	2004 Nov	15577766
[Chronic favus caused by infection with Trichophyton schönleinii].	2004 Oct	16281590
Management of onychomycosis with topicals.	2004 Oct	15450900
Ciclopirox delivery into the human nail plate.	2004 Oct	15349963
Cell cycle arrest at the initiation step of human chromosomal DNA replication causes DNA damage.	2004 Oct 1	15456844
Pharmacotherapy of onychomycosis.	2005 Apr	15934887
In vitro transungual permeation of ciclopirox from a hydroxypropyl chitosan-based, water-soluble nail lacquer.	2005 Jan	15704853
Pharmacoeconomic analysis of sequential treatment pathways in the treatment of onychomycosis.	2005 Jan	15682633
Treatment and prophylaxis of seborrheic dermatitis of the scalp with antipityrosporal 1% ciclopirox shampoo.	2005 Jan	15655141
Topical antifungal drugs for the treatment of onychomycosis: an overview of current strategies for monotherapy and combination therapy.	2005 Jan	15649187
Physicochemical studies on Ciclopirox olamine complexes with divalent metal ions.	2005 Jan 31	15652210
A multicenter, open-label study to assess the safety and efficacy of ciclopirox topical suspension 0.77% in the treatment of diaper dermatitis due to Candida albicans.	2005 Jan-Feb	15696982
Evaluation of the efficacy of ciclopirox 0.77% gel in the treatment of tinea pedis interdigitalis (dermatophytosis complex) in a randomized, double-blind, placebo-controlled trial.	2005 Jul	15985032
In vitro susceptibility of 15 strains of zygomycetes to nine antifungal agents as determined by the NCCLS M38-A microdilution method.	2005 Jul	15982206
Ciclopirox topical solution, 8% combined with oral terbinafine to treat onychomycosis: a randomized, evaluator-blinded study.	2005 Jul-Aug	16004022
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Ciclopirox protects mitochondria from hydrogen peroxide toxicity.	2005 Jun	15806112
Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation.	2005 Jun 15	15741220
The safety and efficacy of ciclopirox olamine for the treatment of seborrheic dermatitis.	2005 Mar	15794716
Trichophyton rubrum isolated from aids and human immunodeficiency virus-infected patients in São Paulo, Brazil: antifungal susceptibility and extracellular enzyme production.	2005 Mar	15722629
Genome-wide expression profiling of the response to ciclopirox olamine in Candida albicans.	2005 May	15814599
Oxygen accessibility and iron levels are critical factors for the antifungal action of ciclopirox against Candida albicans.	2005 May	15790671
Ciclopirox nail lacquer 8% for the treatment of onychomycosis: a Canadian perspective.	2005 Sep	16292454

Patents

Sample Use Guides

In Vivo Use Guide

Seborrheic dermatitis: Wet hair and apply approximately 1 teaspoon (5 mL) of LOPROX Shampoo to the scalp. Up to 2 teaspoons (10 mL) may be used for long hair. Lather and leave on hair and scalp for 3 minutes. Rinse off. Treatment should be repeated twice per week for 4 weeks, with a minimum of 3 days between application. Onychomycosis:

Route of Administration: Topical

In Vitro Use Guide

Ciclopirox exhibited the best antifungal activity against S. brevicaulis, with MICs ranging from 1 to 8mg/l. Mode, MIC50, and MIC90 amounted to 4mg/l.

Name

Type

Language

CICLOPIROX

Official Name

English

HOE-296B

Code

English

CICLOPIROX [USP-RS]

Common Name

English

CICLOPIROX [MI]

Common Name

English

2(1H)-PYRIDINONE, 6-CYCLOHEXYL-1-HYDROXY-4-METHYL-

Systematic Name

English

LOPROX

Brand Name

English

6-CYCLOHEXYL-1-HYDROXY-4-METHYL-2(1H)-PYRIDINONE

Systematic Name

English

CICLOPIROX [MART.]

Common Name

English

CYCLOPIROX

Common Name

English

PENLAC

Brand Name

English

CICLOPIROX [USAN]

Common Name

English

CICLOPIROX [ORANGE BOOK]

Common Name

English

CICLOPIROX [VANDF]

Common Name

English

CICLOPIROX [USP MONOGRAPH]

Common Name

English

Ciclopirox [WHO-DD]

Common Name

English

CICLOPIROX [EP MONOGRAPH]

Common Name

English

ciclopirox [INN]

Common Name

English

HOE 296B

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

629718