DT-Web

DB00735 - Naftifine


Identification
Name Naftifine
Accession Number DB00735 (APRD01131)
Type small molecule
Description Naftifine is a synthetic, broad spectrum, antifungal agent and allylamine derivative 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 287.3981
Groups approved
Monoisotopic Weight 287.167399677
Pharmacology
Indication 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.
Mechanism of action 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.
Absorption Following single topical applications of 3H-labeled naftifine gel 1% to the skin of healthy subjects, up to 4.2% of the applied dose was absorbed.
Protein binding Not Available
Biotransformation Not Available
Route of elimination Naftifine and/or its metabolites are excreted via the urine and feces with a half-life of approximately two to three days.
Toxicity Not Available
Affected organisms
  • Yeast and other fungi
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Squalene monooxygenase
Name Squalene monooxygenase
Gene Name SQLE
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Favre B, Ryder NS: Characterization of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents. Antimicrob Agents Chemother. 1996 Feb;40(2):443-7. - Pubmed
  • Vanden Bossche H, Marichal P: Mode of action of anti-Candida drugs: focus on terconazole and other ergosterol biosynthesis inhibitors. Am J Obstet Gynecol. 1991 Oct;165(4 Pt 2):1193-9. - Pubmed
  • 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
  • Ryder NS, Dupont MC: Inhibition of squalene epoxidase by allylamine antimycotic compounds. A comparative study of the fungal and mammalian enzymes. Biochem J. 1985 Sep 15;230(3):765-70. - Pubmed
  • Ryder NS, Frank I: Interaction of terbinafine with human serum and serum proteins. J Med Vet Mycol. 1992;30(6):451-60. - Pubmed
DTHybrid score 0.8882

Predictions


Id Partner name Gene Name Score
7196 Squalene monooxygenase ERG1 0.8882
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0208
6124 Carbonic anhydrase 5B, mitochondrial CA5B 0.0176
3811 Cytochrome P450 19A1 CYP19A1 0.0176
6131 Carbonic anhydrase 14 CA14 0.0161
997 Protein kinase C beta type PRKCB 0.0156
6122 Carbonic anhydrase 3 CA3 0.0153
20 Prostaglandin G/H synthase 1 PTGS1 0.0152
6123 Carbonic anhydrase 5A, mitochondrial CA5A 0.0147
2408 Tyrosine-protein kinase SYK SYK 0.0144
1970 Protein kinase C alpha type PRKCA 0.0142
3007 Carbonic anhydrase 12 CA12 0.0137
4205 Carbonic anhydrase 9 CA9 0.0137
4924 Cytochrome P450 2C8 CYP2C8 0.013
6126 Carbonic anhydrase 7 CA7 0.0128
6016 Cytochrome P450 2C19 CYP2C19 0.0126
4200 Cytochrome P450 1A2 CYP1A2 0.0124
4757 Cytochrome P450 2C9 CYP2C9 0.012
4119 Cytochrome P450 2D6 CYP2D6 0.0117
2236 Casein kinase II subunit alpha CSNK2A1 0.011
4512 Cytochrome P450 3A4 CYP3A4 0.0105
592 Carbonic anhydrase 4 CA4 0.0102
6263 cAMP-dependent protein kinase catalytic subunit alpha PRKACA 0.0097
295 Carbonic anhydrase 1 CA1 0.0097
1024 Solute carrier family 22 member 11 SLC22A11 0.0088
357 Carbonic anhydrase 2 CA2 0.008
6024 Cytochrome P450 1A1 CYP1A1 0.0074
1729 Solute carrier family 22 member 6 SLC22A6 0.007
6013 Cytochrome P450 2E1 CYP2E1 0.007
↑