DT-Web

DB01091 - Butenafine


Identification
Name Butenafine
Accession Number DB01091 (APRD00833)
Type small molecule
Description Butenafine hydrochloride is a synthetic benzylamine antifungal agent. Butenafine works by inhibiting the synthesis of sterols by inhibiting squalene epoxidase, an enzyme responsible for the creation of sterols needed in fungal cell membranes.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 317.4672
Groups approved
Monoisotopic Weight 317.214349869
Pharmacology
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.
Mechanism of action Although the mechanism of action has not been fully established, it has been suggested that butenafine, like allylamines, interferes with sterol biosynthesis (especially ergosterol) by inhibiting squalene monooxygenase, an enzyme responsible for converting squalene to 2,3-oxydo squalene. 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. Blockage of squalene monooxygenase also leads to a subsequent accumulation of squalene. When a high concentration of squalene is reached, it is thought to have an effect of directly kill fungal cells.
Absorption The total amount absorbed through the skin into the systemic circulation has not been quantified.
Protein binding Not Available
Biotransformation The primary metabolite in urine was formed through hydroxylation at the terminal t-butyl side-chain.
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • 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
  • 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
  • Singal A: Butenafine and superficial mycoses: current status. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):999-1005. - Pubmed
  • Ramam M, Prasad HR, Manchanda Y, Khaitan BK, Banerjee U, Mukhopadhyaya A, Shetty R, Gogtay JA: Randomised controlled trial of topical butenafine in tinea cruris and tinea corporis. Indian J Dermatol Venereol Leprol. 2003 Mar-Apr;69(2):154-8. - Pubmed
  • Iwatani W, Arika T, Yamaguchi H: Two mechanisms of butenafine action in Candida albicans. Antimicrob Agents Chemother. 1993 Apr;37(4):785-8. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - 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
↑