Efinaconazole

• CAS: 164650-44-6
• Catalog Number: ACM164650446
• Category: Inhibitors
• Molecular Weight: 348.39
• Molecular Formula: C18H22F2N4O
• Description: Efinaconazole is a triazole antifungal. It is approved for use in Canada and the USA as a 10% topical solution for the treatment of onychomycosis (fungal infection of the nail). Efinaconazole acts as a 14α-demethylase inhibitor. Efinaconazole inhibits fungal lanosterol 14α-demethylase involved in the biosynthesis of ergosterol, a constituent of fungal cell membranes. Efinaconazole has been shown to be active against isolates of the following microorganisms, both in vitro and in clinical infections. Efinaconazole exhibits in vitro minimum inhibitory concentrations (MICs) of 0.06 μg/mL or less against most ( ≥ 90%) isolates of the following microorganisms: Trichophyton rubrum; Trichophyton mentagrophytes.
• Synonyms: KP103; KP-103; KP 103; CTK5J2975; AGJ95634; KB145948; Efinaconazole; trade name: Jublia
• IUPAC Name: (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
• Canonical SMILES: C[C@@H](N1CCC(CC1)=C)[C@@](O)(C2=CC=C(F)C=C2F)CN3N=CN=C3
• InChI: 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
• InChI Key: NFEZZTICAUWDHU-RDTXWAMCSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: Efinaconazole (KP-103) is a triazole antifungal agent and againsts T. mentagrophytes SM-110 and C. albicans ATCC 10231 with MICs of 0.0039 μg/mL and 0.00098 μg/mL, respectively.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 62.05; H, 6.36; F, 10.91; N, 16.08; O, 4.59
• Exact Mass: 348.1762
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: The in vitro antifungal activity of efinaconazole, a novel triazole antifungal, was evaluated in recent clinical isolates of Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans, common causative onychomycosis pathogens. Efinaconazole MICs against T. rubrum and T. mentagrophytes ranged from ≤ 0.002 to 0.06 μg/ml, with 90% of isolates inhibited (MIC90) at 0.008 and 0.015 μg/ml, respectively. Efinaconazole MICs against 105 C. albicans isolates ranged from ≤ 0.0005 to >0.25 μg/ml, with 50% of isolates inhibited (MIC50) by 0.001 and 0.004 μg/ml at 24 and 48 h, respectively. The activity of efinaconazole was further evaluated in another 8 dermatophyte, 15 nondermatophyte, and 10 yeast species (a total of 109 isolates from research repositories). Efinaconazole was active against Trichophyton, Microsporum, Epidermophyton, Acremonium, Fusarium, Paecilomyces, Pseudallescheria, Scopulariopsis, Aspergillus, Cryptococcus, Trichosporon, and Candida and compared favorably to other antifungal drugs. In conclusion, efinaconazole is a potent antifungal with a broad spectrum of activity that may have clinical applications in onychomycosis and other mycoses.; Reference: Antimicrob Agents Chemother. 2013 Apr;57(4):1610-6. https://pubmed.ncbi.nlm.nih.gov/23318803/
• In Vivo Activity: Efinaconazole solution and topical formulation vehicle administered dermally to mice (13weeks), rats (6months) and minipigs (9months) produced transient erythema, minimal to modest hyperkeratosis, and mild microscopic skin inflammation. The liver was the target organ of systemic toxicity; reversible, minimal to moderate vacuolated changes were noted in the rat dermal study at 15 and 50mg/kg/day. No systemic toxicity was observed in mice and minipigs, at approximate high dermal doses of 930 and 170mg/kg/day, respectively. Daily subcutaneous injection of propylene glycol vehicle or efinaconazole to rats for 6months produced severe local inflammation and systemic spread, evidenced by peritoneal adhesions, spinal cord necrosis and urinary tract disease. Mortalities occurred in all groups but were increased at the high dose (30 or 40mg/kg/day), suggesting that vehicle effects were exacerbated by efinaconazole. Efinaconazole was not carcinogenic in a 2-year mouse dermal study and was not genotoxic. In conclusion, efinaconazole demonstrated low/moderate toxicity, consistent with other azole antifungals, and high safety margins for topical onychomycosis therapy.; Reference: Regul Toxicol Pharmacol. 2014 Oct;70(1):242-53. https://pubmed.ncbi.nlm.nih.gov/25038564/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).