| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:07:24 |
| Primary Accession Number |
DB01091 |
| Secondary Accession Number |
|
| Name |
Butenafine |
| Drug Type |
|
| Description |
Butenafine hydrochloride is a synthetic benzylamine antifungal agent. Butenafine works by inhibiting the synthesis of ergosterol by inhibiting squalene epoxidase, an enzyme responsible for the creation of sterols needed in fungal cell membranes. |
| Synonyms |
- Butenafina [INN-Spanish]
- Butenafine HCL
- Butenafine [INN]
- Butenafine hydrochloride
- Butenafinum [INN-Latin]
|
| Brand Names |
- Lotrimin Ultra
- Mentax
- Mentax-tc
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
1-(4-tert-butylphenyl)-N-methyl-N-(naphthalen-1-ylmethyl)methanamine |
| Chemical Formula |
C23H27N |
| Chemical Structure |
 |
| CAS Registry Number |
101828-21-1 |
| InChI Identifier |
InChI=1/C23H27N/c1-23(2,3)21-14-12-18(13-15-21)16-24(4)17-20-10-7-9-19-8-5-6-11-22(19)20/h5-15H,16-17H2,1-4H3 |
| InChI Key |
ABJKWBDEJIDSJZ-UHFFFAOYAT |
| KEGG Drug |
Not Available |
| KEGG Compound |
C08067  |
| PubChem Compound |
2484  |
| PubChem Substance |
10267  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA448698  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02231063  |
| RxList Link |
http://www.rxlist.com/cgi/generic2/butenafine.htm  |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Butenafine  |
| FDA Label |
|
| Material Safety Data Sheet (MSDS) |
Not Available |
| Synthesis Reference |
Not Available |
| Average Molecular Weight |
317.4672 |
| Monoisotopic Molecular Weight |
317.2143 |
| State |
Solid |
| Melting Point |
Not Available |
| Experimental Water Solubility |
Slightly soluble (HCl salt)
Source: PhysProp
|
| Predicted Water Solubility |
7.56e-05 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
6.6
Source: PhysProp
|
| Predicted LogP |
5.86
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-6.62
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
CN(CC1=CC=C(C=C1)C(C)(C)C)CC1=CC=CC2=CC=CC=C12 |
| Canonical SMILES |
CN(CC1=CC=C(C=C1)C(C)(C)C)CC1=CC=CC2=CC=CC=C12 |
| Drug Category |
|
| ATC Codes |
|
| AHFS Codes |
Not Available |
| Indication |
For the topical treatment of the following dermatologic infections: tinea (pityriasis) versicolor due to M. furfur, interdigital tinea pedis (athlete’s foot), tinea corporis (ringworm) and tinea cruris (jock itch) due to E. floccosum, T. mentagrophytes, T. rubrum, and T. tonsurans. |
| Pharmacology |
Butenafine is an antifungal agent that acts by inhibiting squalene epoxidase, thus blocking the biosynthesis of ergosterol, an essential component of fungal cell membranes. It is mainly active against dermatophytes and has superior fungicidal activity against this group of fungi when compared to that of terbinafine, naftifine, tolnaftate, clotrimazole, and bifonazole. It is active also against Candida albicans and this activity is superior to that of terbinafine and naftifine. Butenafine also generates low MICs for Cryptococcus neoformans and Aspergillus spp. as well. |
| Mechanism of Action |
Like allylamines, butenafine inhibits ergosterol biosynthesis by blocking squalene epoxidation. 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. |
| Absorption |
The total amount absorbed through the skin into the systemic circulation has not been quantified. |
| Toxicity |
Not Available |
| Protein Binding |
Not Available |
| Biotransformation |
The primary metabolite in urine was formed through hydroxylation at the terminal t-butyl side-chain. |
| Half Life |
Following topical application, a biphasic decline of plasma butenafine concentrations was observed with the half-lives estimated to be 35 hours initial and over 150 hours terminal. |
| Dosage Forms |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
Not Available
|
| Food Interactions |
Not Available
|
| Pathways |
Not Available
|
| General References |
- Wikipedia

- RxList

|
| Organisms Affected |
|
| Targets |
- Squalene monooxygenase
|
|
Drug Target 1
[top]
|
| Target 1 ID |
634 |
| Target 1 Name |
Squalene monooxygenase |
| Target 1 Synonyms |
- EC 1.14.99.7
- SE
- Squalene epoxidase
|
| Target 1 Gene Name |
SQLE |
| Target 1 Protein Sequence |
>Squalene monooxygenase
MWTFLGIATFTYFYKKFGDFITLANREVLLCVLVFLSLGLVLSYRCRHRNGGLLGRQRSG
SQFALFSDILSGLPFIGFFWAKSPPESENKEQLGARRRRKGTNISETSLIGTAACTSTSS
QNDPEVIIVGAGVLGSALVAVLSRDGRKVTVIERDLKEPDRIVGEFLQPGGYHVLKDLGL
GDTVEGLDAQVVNGYMIHDQESKSEVQIPYPLSENNQVQSGRAFHHGRFIMSLRKAAMAE
PNAKFIEGVVLQLLEEDDVVMGVQYKDKETGDIKELHAPLTVVADGLFSKFRKSLVSNKV
SVSSHFVGFLMKNAPQFKANHAELILANPSPVLIYRISSSETRVLVDIRGEMPRNLREYM
VEKIYPQIPDHLKEPFLEATDNSHLRSMLASFLPPSSVKKRGVLLLGDAYNMRHPLTGGG
MTVAFKDIKLWRKLLKGIPDLYDDAAIFEANKSFYWARKTSHSFVVNILAQALYELFSAT
DDSLHQLRKACFLYFKLGGECVAGPVGLLSVLSPNPLALIGHFFAVAIYAVYFCFKSEPW
ITKPRALLSSSAVLYKACSVIFPLIYSEMKYMVH
|
| Target 1 Number of Residues |
583 |
| Target 1 Molecular Weight |
63940 |
| Target 1 Theoretical pI |
9.12 |
| Target 1 GO Classification |
|
Function
|
catalytic activity
oxidoreductase activity |
|
Process
|
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport |
|
Component
|
| Not Available |
|
| Target 1 General Function |
Coenzyme transport and metabolism |
| Target 1 Specific Function |
Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway |
| Target 1 Pathways |
| Name |
SMPDB Link |
KEGG Link |
| Biosynthesis of steroids |
|
map00100  |
| Terpenoid biosynthesis |
|
map00900  |
|
| Target 1 Reactions |
- squalene + AH2 + O2 = (S)-squalene-2,3-epoxide + A + H2O
|
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 20-40
- 61-81
- 123-143
- 546-566
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
2443316  |
| Target 1 UniProtKB/Swiss-Prot ID |
Q14534  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
ERG1_HUMAN  |
| Target 1 PDB ID |
Not Available |
| Target 1 Cellular Location |
- Microsome
- microsomal membrane
- multi-pass membrane protein
|
| Target 1 Gene Sequence |
>1725 bp
ATGTGGACTTTTCTGGGCATTGCCACTTTCACCTATTTTTATAAGAAGTTCGGGGACTTC
ATCACTTTGGCCAACAGGGAGGTCCTGTTGTGCGTGCTGGTGTTCCTCTCGCTGGGCCTG
GTGCTCTCCTACCGCTGTCGCCACCGAAACGGGGGTCTCCTCGGGCGCCAGCGGAGCGGC
TCCCAGTTCGCCCTCTTCTCGGATATTCTCTCAGGCCTGCCTTTCATTGGCTTCTTCTGG
GCCAAATCCCCCCCTGAATCAGAAAATAAGGAGCAGCTCGGGGCCAGGAGGCGCAGAAAA
GGAACCAATATTTCAGAAACAAGCTTAATAGGAACAGCTGCCTGTACATCAACATCTTCT
CAGAATGACCCAGAAGTTATCATCGTGGGAGCTGGCGTGCTTGGCTCTGCTTTGGTAGCT
GTGCTTTCCAGAGATGGAAGAAAGGTGACAGTCATTGAGAGAGACTTAAAAGAGCCTGAC
AGAATAGTTGGAGAATTCCTGCAGCCGGGTGGTTATCATGTTCTCAAAGACCTTGGTCTT
GGAGATACAGTGGAAGGTCTTGATGCCCAGGTTGTAAATGGTTACATGATTCATGATCAG
GAAAGCAAATCAGAGGTTCAGATTCCTTACCCTCTGTCAGAAAACAATCAAGTGCAGAGT
GGAAGAGCTTTCCATCACGGAAGATTCATCATGAGTCTCCGGAAAGCAGCTATGGCAGAG
CCCAATGCAAAGTTTATTGAAGGTGTTGTGTTACAGTTATTAGAGGAAGATGATGTTGTG
ATGGGAGTTCAGTACAAGGATAAAGAGACTGGAGATATCAAGGAACTCCATGCTCCACTG
ACTGTTGTTGCAGATGGGCTTTTCTCCAAGTTCAGGAAAAGCCTGGTCTCCAATAAAGTT
TCTGTATCATCTCATTTTGTTGGCTTTCTTATGAAGAATGCACCACAGTTTAAAGCAAAT
CATGCTGAACTTATTTTAGCTAACCCGAGTCCAGTTCTCATCTACCGGATTTCATCCAGT
GAAACTCGAGTACTTGTTGACATTAGAGGAGAAATGCCAAGGAATTTAAGAGAATACATG
GTTGAAAAAATTTACCCACAAATACCTGATCACCTGAAAGAACCATTCTTAGAAGCCACT
GACAATTCTCATCTGAGGTCCATGCTAGCAAGCTTCCTTCCTCCTTCATCAGTGAAGAAA
CGAGGTGTTCTTCTTTTGGGAGACGCATATAATATGAGGCATCCACTTACTGGTGGAGGA
ATGACTGTTGCTTTTAAAGATATAAAACTATGGAGAAAACTGCTAAAGGGTATCCCTGAC
CTTTATGATGATGCAGCTATTTTCGAGGCCAACAAATCATTTTACTGGGCAAGAAAAACA
TCTCATTCCTTTGTCGTGAATATCCTTGCTCAGGCTCTTTATGAATTATTTTCTGCCACA
GATGATTCCCTGCATCAACTAAGAAAAGCCTGTTTTCTTTATTTCAAACTTGGTGGCGAA
TGTGTTGCGGGTCCTGTTGGGCTGCTTTCTGTATTGTCTCCTAACCCTCTAGCTTTAATT
GGACACTTCTTTGCTGTTGCAATCTATGCCGTGTATTTTTGCTTTAAGTCAGAACCTTGG
ATTACAAAACCTCGAGCCCTTCTCAGTAGTAGTGCTGTATTGTACAAAGCGTGTTCTGTA
ATATTTCCTCTAATTTACTCAGAAATGAAGTATATGGTTCATTAA
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
SQLE  |
| Target 1 GenAtlas ID |
SQLE  |
| Target 1 HGNC ID |
HGNC:11279  |
| Target 1 Chromosome Location |
8 |
| Target 1 Locus |
8q24.1 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Nakamura Y, Sakakibara J, Izumi T, Shibata A, Ono T: Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells. J Biol Chem. 1996 Apr 5;271(14):8053-6. [PubMed
]
- Nagai M, Sakakibara J, Wakui K, Fukushima Y, Igarashi S, Tsuji S, Arakawa M, Ono T: Localization of the squalene epoxidase gene (SQLE) to human chromosome region 8q24.1. Genomics. 1997 Aug 15;44(1):141-3. [PubMed
]
|
| Target 1 Drug References |
- Mukherjee PK, Leidich SD, Isham N, Leitner I, Ryder NS, Ghannoum MA: Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine. Antimicrob Agents Chemother. 2003 Jan;47(1):82-6. [PubMed
]
- Gao PH, Cao YB, Xu Z, Zhang JD, Zhang WN, Wang Y, Gu J, Cao YY, Li RY, Jia XM, Jiang YY: In vitro antifungal activity of ZJ-522, a new triazole restructured from fluconazole and butenafine, against clinically important fungi in comparison with fluconazole and butenafine. Biol Pharm Bull. 2005 Aug;28(8):1414-7. [PubMed
]
|