NAFTIFINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H21N
Molecular Weight	287.3981
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C\C=C\C1=CC=CC=C1)CC2=CC=CC3=CC=CC=C23

InChI

InChIKey=OZGNYLLQHRPOBR-DHZHZOJOSA-N

InChI=1S/C21H21N/c1-22(16-8-11-18-9-3-2-4-10-18)17-20-14-7-13-19-12-5-6-15-21(19)20/h2-15H,16-17H2,1H3/b11-8+

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00735
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/naftin.html

Naftifine is a synthetic, broad spectrum, antifungal agent and allylamine derivative. The following in vitro data are available, but their clinical significance is unknown. Naftifine has been shown to exhibit fungicidal activity in vitro against a broad spectrum of organisms including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Microsporum canis, Microsporum audouini, and Microsporum gypseum; and fungistatic activity against Candida species including Candida albicans. However it is only used to treat the organisms listed in the indications. Although the exact mechanism of action against fungi is not known, naftifine appears to interfere with sterol biosynthesis by inhibiting the enzyme squalene 2,3-epoxidase. This inhibition of enzyme activity results in decreased amounts of sterols, especially ergosterol, and a corresponding accumulation of squalene in the cells. Naftifine is used for the topical treatment of tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans and Epidermophyton floccosum. Marketed as Naftin.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Squalene monooxygenase 10 Target ID: CHEMBL3592 Sources: http://www.drugbank.ca/drugs/DB00735	Inhibitor 8297
Squalene monooxygenase 10 Target ID: CHEMBL2364679 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8834895	Inhibitor 8297	114.6 nM [IC50]
Squalene monooxygenase 10 Target ID: Q92206 Gene ID: 3646458\|\|\|3646509 Gene Symbol: ERG1 Target Organism: Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast) Sources: https://www.ncbi.nlm.nih.gov/pubmed/3877503	Inhibitor 8297	1.1 µM [Ki]
Lymphoma cell line 2 Target ID: CHEMBL614114 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26504016	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tinea pedis 28 Sources: https://www.drugs.com/pro/naftin.html	Curative		Approved 8429	Naftin Approved Use Naftin Cream is an allylamine antifungal indicated for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organism Trichophyton rubrum. Launch Date 2012
Tinea corporis 19 Sources: https://www.drugs.com/pro/naftin.html	Curative		Approved 8429	Naftin Approved Use Naftin Cream is an allylamine antifungal indicated for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organism Trichophyton rubrum. Launch Date 2012

C_max

Value	Dose	Analyte	Population
9.21 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	8.1 g single, topical dose: 8.1 g route of administration: Topical experiment type: SINGLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
12.7 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	8.1 g 1 times / day multiple, topical dose: 8.1 g route of administration: Topical experiment type: MULTIPLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
7 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	6.4 g single, topical dose: 6.4 g route of administration: Topical experiment type: SINGLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	6.4 g 1 times / day multiple, topical dose: 6.4 g route of administration: Topical experiment type: MULTIPLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.6 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	2.3 g single, topical dose: 2.3 g route of administration: Topical experiment type: SINGLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
3.31 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	2.3 g 1 times / day multiple, topical dose: 2.3 g route of administration: Topical experiment type: MULTIPLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
138 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	8.1 g single, topical dose: 8.1 g route of administration: Topical experiment type: SINGLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
192 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	8.1 g 1 times / day multiple, topical dose: 8.1 g route of administration: Topical experiment type: MULTIPLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: UNKNOWN
117 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	6.4 g single, topical dose: 6.4 g route of administration: Topical experiment type: SINGLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
204 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	6.4 g 1 times / day multiple, topical dose: 6.4 g route of administration: Topical experiment type: MULTIPLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
49.8 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	2.3 g single, topical dose: 2.3 g route of administration: Topical experiment type: SINGLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
52.4 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	2.3 g 1 times / day multiple, topical dose: 2.3 g route of administration: Topical experiment type: MULTIPLE co-administered:	NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.5 day DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019356s008,019599s014,204286s003lbl.pdf	6.4 g single, topical dose: 6.4 g route of administration: Topical experiment type: SINGLE co-administered:		NAFTIFINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 % 1 times / day multiple, topical Recommended Dose: 2 %, 1 times / day Route: topical Route: multiple Dose: 2 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019599s013lbl.pdf	unhealthy, 9 (2-18) n = 116 Health Status: unhealthy Condition: tinea pedis \| tinea cruris \| tinea corporis Age Group: 9 (2-18) Sex: M+F Population Size: 116 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019599s013lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019599s013lbl.pdf
2 % 1 times / day multiple, topical Recommended Dose: 2 %, 1 times / day Route: topical Route: multiple Dose: 2 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019599s013lbl.pdf	unhealthy, adult n = 400 Health Status: unhealthy Condition: tinea pedis \| tinea cruris \| tinea corporis Age Group: adult Sex: M+F Population Size: 400 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019599s013lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019599s013lbl.pdf
2 % 1 times / day multiple, topical Recommended Dose: 2 %, 1 times / day Route: topical Route: multiple Dose: 2 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204286Orig1s000MedR.pdf Page: 1010, 3015, and 3016	unhealthy n = 1747 Health Status: unhealthy Condition: tinea pedis Sex: M+F Population Size: 1747 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204286Orig1s000MedR.pdf Page: 1010, 3015, and 3016	Disc. AE: Application site fissure, Hypersensitivity... AEs leading to discontinuation/dose reduction: Application site fissure (grade 3-4) Hypersensitivity (grade 2-3) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204286Orig1s000MedR.pdf Page: 1010, 3015, and 3016

AEs

AE	Significance	Dose	Population
Hypersensitivity	grade 2-3 Disc. AE	2 % 1 times / day multiple, topical Recommended Dose: 2 %, 1 times / day Route: topical Route: multiple Dose: 2 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204286Orig1s000MedR.pdf Page: 1010, 3015, and 3016	unhealthy n = 1747 Health Status: unhealthy Condition: tinea pedis Sex: M+F Population Size: 1747 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204286Orig1s000MedR.pdf Page: 1010, 3015, and 3016
Application site fissure	grade 3-4 Disc. AE	2 % 1 times / day multiple, topical Recommended Dose: 2 %, 1 times / day Route: topical Route: multiple Dose: 2 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204286Orig1s000MedR.pdf Page: 1010, 3015, and 3016	unhealthy n = 1747 Health Status: unhealthy Condition: tinea pedis Sex: M+F Population Size: 1747 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204286Orig1s000MedR.pdf Page: 1010, 3015, and 3016

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 270 UGT 192

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/3964331/	yes
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/3964331/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7451	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7451
ZINC	ZINC000001530977	http://zinc15.docking.org/substances/ZINC000001530977

PubMed

Title	Date	PubMed
In vitro activity of naftifine, a new antifungal agent.	1981 Mar	7247366
Effect of the antimycotic drug naftifine on growth of and sterol biosynthesis in Candida albicans.	1984 Apr	6375557
[Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent].	1991 Feb	2056447
Effects of naftifine and terbinafine, two allylamine antifungal drugs, on selected functions of human polymorphonuclear leukocytes.	1994 Nov	7872755
Azole antifungal agents related to naftifine and butenafine.	2000 Jun	10909187

Patents

Sample Use Guides

In Vivo Use Guide

For topical use only. NAFTIN Cream is not for ophthalmic, oral or intravaginal use. Apply a thin layer of NAFTIN Cream once-daily to the affected areas plus a ½ inch margin of healthy surrounding skin for 2 weeks.

Route of Administration: Topical

In Vitro Use Guide

The anti-tumor apoptotic effect of naftifine at doses ranging from 0.1-200 uM was investigated on two human and one murine lymphoma. Naftifine significantly reduced cell viability in all tested myeloma and lymphoma cell lines in a dose-dependent manner.

Name

Type

Language

NAFTIFINE

Official Name

English

NAFT-500

Brand Name

English

Naftifine [WHO-DD]

Common Name

English

NAFTIFINE [MI]

Common Name

English

NAFTIFINE [VANDF]

Common Name

English

AW-105-843

Code

English

naftifine [INN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QD01AE22