Drug Information

Drug (ID: DG01054) and It's Reported Resistant Information

• Name: Efinaconazole
• Synonyms: EFINACONAZOLE; 164650-44-6; (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol; KP-103; JUBLIA; UNII-J82SB7FXWB; KP103; J82SB7FXWB; CHEBI:82718; 164905-19-5; (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylidenepiperidin-1-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol; Kp 103; Efinaconazole [USAN:INN]; efinaconazol; efinaconazolum; Clenafin; IDP-108; Clenafin (TN); Jublia (TN); Efinaconazole(KP-103); Efinaconazole; KP-103; SCHEMBL300738; ZINC6251; CHEMBL2103877; Efinaconazole (JAN/USAN/INN); C18H22F2N4O; HSDB 8341; DTXSID40167787; BCP11665; EX-A2643; 2856AH; MFCD00936406; s5025; AKOS027323571; CCG-268012; CS-3500; DB09040; NCGC00390702-01; NCGC00390702-02; NCGC00390702-03; (2R,3R)-2-(2,4-Difluorofenil)-3-(4-metilenopiperidin-1-il)-1-(1H-1,2,4-triazin-1-il)butan-2-ol; AC-30630; AS-30126; HY-15660; D10021; A854585; Q21011225; (2R, 3R)-2-(2,4-Difluorophenyl)-3-(4-methylenepiperidyl)-1-(1,2,4-triazolyl)butan-2-ol; (2R,3R)-2-(2,4-Difluorophenyl)-3-(4-methylene-1-piperidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol; (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylene-1-piperidyl)-1-(1,2,4-triazol-1-yl)butan-2-ol; (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)butane-2-ol; (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidino)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol; (alphaR,betaR)-alpha-(2,4-Difluorophenyl)-beta-methyl-4-methylene-alpha-(1H-1,2,4-triazol-1-ylmethyl)-1-piperidineethanol; 1-Piperidineethanol, alpha-(2,4-difluorophenyl)-beta-methyl-4-methylene-alpha-(1H-1,2,4-triazol-1- ylmethyl)-, (alphaR,betaR)-; 1-Piperidineethanol, alpha-(2,4-difluorophenyl)-beta-methyl-4-methylene-alpha-(1H-1,2,4-triazol-1-ylmethyl)-, (alphaR,betaR)-
• Indication:
  In total 1 Indication(s)
  Fungal infection [ICD-11: 1F29-1F2F]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Superficial mycoses [ICD-11: 1F2Z]; [1]
• Target: Candida Cytochrome P450 51 (Candi ERG11); CP51_CANAL; [1]
• Formula: C18H22F2N4O
• IsoSMILES: C[C@H]([C@](CN1C=NC=N1)(C2=C(C=C(C=C2)F)F)O)N3CCC(=C)CC3
• InChI: 1S/C18H22F2N4O/c1-13-5-7-23(8-6-13)14(2)18(25,10-24-12-21-11-22-24)16-4-3-15(19)9-17(16)20/h3-4,9,11-12,14,25H,1,5-8,10H2,2H3/t14-,18-/m1/s1
• InChIKey: NFEZZTICAUWDHU-RDTXWAMCSA-N
• PubChem CID: 489181
• ChEBI ID: CHEBI:82718
• TTD Drug ID: D0G4BI
• DrugBank ID: DB09040

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Dermatophytosis [ICD-11: 1F28]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Sterol 14-alpha demethylase cyp51A (CYP51A) [2]

• Sensitive Disease: Tinea unguium [ICD-11: 1F28.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Antifungal susceptibility assay
• Mechanism Description: The expression of?cyp51A?mRNA was induced by the addition of the azole antifungal drug efinaconazole, whereas no such induction was detected for?cyp51B, suggesting that Cyp51A functions as an azole-responsive Cyp51 isozyme. To explore the contribution of Cyp51A to susceptibility to azole drugs, the neomycin phosphotransferase (nptII) gene cassette was inserted into the?cyp51A?3'-untranslated region of deltaku80?to destabilize the mRNA of?cyp51A. In this mutant, the induction of?cyp51A?mRNA expression by efinaconazole was diminished. The minimum inhibitory concentration for several azole drugs of this strain was reduced, suggesting that dermatophyte Cyp51A contributes to the tolerance for azole drugs.

References

• Ref 1: Antifungal resistance in Superficial mycoses .J Dermatolog Treat. 2021 Jun 16:1-25. doi: 10.1080/09546634.2021.1942421. Online ahead of print. 10.1080/09546634.2021.1942421
• Ref 2: An efficient gene targeting system using deltaku80 and functional analysis of Cyp51A in Trichophyton rubrum. AMB Express. 2024 Aug 31;14(1):96.