Synonym
KP103; KP-103; KP 103; CTK5J2975; AGJ95634; KB145948; Efinaconazole; trade name: Jublia.
IUPAC/Chemical Name
(2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
InChi Key
NFEZZTICAUWDHU-RDTXWAMCSA-N
InChi Code
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
SMILES Code
C[C@@H](N1CCC(CC1)=C)[C@@](O)(C2=CC=C(F)C=C2F)CN3N=CN=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
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.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO.
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
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.
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/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
61.0 |
175.09 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
348.39
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Hur MS, Park M, Jung WH, Lee YW. Evaluation of drug susceptibility test for Efinaconazole compared with conventional antifungal agents. Mycoses. 2019 Mar;62(3):291-297. doi: 10.1111/myc.12870. Epub 2018 Dec 17. PMID: 30427072.
2. Jo Siu WJ, Tatsumi Y, Senda H, Pillai R, Nakamura T, Sone D, Fothergill A. Comparison of in vitro antifungal activities of efinaconazole and currently available antifungal agents against a variety of pathogenic fungi associated with onychomycosis. Antimicrob Agents Chemother. 2013 Apr;57(4):1610-6. doi: 10.1128/AAC.02056-12. Epub 2013 Jan 14. PMID: 23318803; PMCID: PMC3623347.
3. . Jo W, Glynn M, Nejishima H, Sanada H, Minowa K, Calvarese B, Senda H, Pillai R, Mutter L. Nonclinical safety assessment of Efinaconazole Solution (10%) for onychomycosis treatment. Regul Toxicol Pharmacol. 2014 Oct;70(1):242-53. doi: 10.1016/j.yrtph.2014.07.012. Epub 2014 Jul 16. PMID: 25038564.
4. Tatsum Y, Yokoo M, Arika T, Yamaguchi H. KP-103, a novel triazole derivative, is effective in preventing relapse and successfully treating experimental interdigital tinea pedis and tinea corporis in guinea pigs. Microbiol Immunol. 2002;46(7):425-32. doi: 10.1111/j.1348-0421.2002.tb02716.x. PMID: 12222928.
In vitro protocol:
1. Hur MS, Park M, Jung WH, Lee YW. Evaluation of drug susceptibility test for Efinaconazole compared with conventional antifungal agents. Mycoses. 2019 Mar;62(3):291-297. doi: 10.1111/myc.12870. Epub 2018 Dec 17. PMID: 30427072.
2. Jo Siu WJ, Tatsumi Y, Senda H, Pillai R, Nakamura T, Sone D, Fothergill A. Comparison of in vitro antifungal activities of efinaconazole and currently available antifungal agents against a variety of pathogenic fungi associated with onychomycosis. Antimicrob Agents Chemother. 2013 Apr;57(4):1610-6. doi: 10.1128/AAC.02056-12. Epub 2013 Jan 14. PMID: 23318803; PMCID: PMC3623347.
In vivo protocol:
1. . Jo W, Glynn M, Nejishima H, Sanada H, Minowa K, Calvarese B, Senda H, Pillai R, Mutter L. Nonclinical safety assessment of Efinaconazole Solution (10%) for onychomycosis treatment. Regul Toxicol Pharmacol. 2014 Oct;70(1):242-53. doi: 10.1016/j.yrtph.2014.07.012. Epub 2014 Jul 16. PMID: 25038564.
2 . Tatsum Y, Yokoo M, Arika T, Yamaguchi H. KP-103, a novel triazole derivative, is effective in preventing relapse and successfully treating experimental interdigital tinea pedis and tinea corporis in guinea pigs. Microbiol Immunol. 2002;46(7):425-32. doi: 10.1111/j.1348-0421.2002.tb02716.x. PMID: 12222928.
1: Gupta AK, Talukder M. Efinaconazole in Onychomycosis. Am J Clin Dermatol. 2022 Mar;23(2):207-218. doi: 10.1007/s40257-021-00660-1. Epub 2021 Dec 13. PMID: 34902110.
2: Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. Efinaconazole. 2018 Dec 3. PMID: 29999786.
3: Poulakos M, Grace Y, Machin JD, Dorval E. Efinaconazole and Tavaborole. J Pharm Pract. 2017 Apr;30(2):245-255. doi: 10.1177/0897190016630904. Epub 2016 Jul 8. PMID: 26873506.
4: Vlahovic TC, Gupta AK. Efinaconazole topical solution (10%) for the treatment of onychomycosis in adult and pediatric patients. Expert Rev Anti Infect Ther. 2022 Jan;20(1):3-15. doi: 10.1080/14787210.2021.1939011. Epub 2021 Jun 30. PMID: 34106031.
5: Lipner SR, Scher RK. Efinaconazole in the treatment of onychomycosis. Infect Drug Resist. 2015 Jun 1;8:163-72. doi: 10.2147/IDR.S69596. PMID: 26082652; PMCID: PMC4459619.
6: Lipner SR, Scher RK. Onychomycosis: Treatment and prevention of recurrence. J Am Acad Dermatol. 2019 Apr;80(4):853-867. doi: 10.1016/j.jaad.2018.05.1260. Epub 2018 Jun 28. PMID: 29959962.
7: Pollak RA. Efinaconazole topical solution, 10%: the development of a new topical treatment for toenail onychomycosis. J Am Podiatr Med Assoc. 2014 Nov;104(6):568-73. doi: 10.7547/8750-7315-104.6.568. PMID: 25514267.
8: Gupta AK, Paquet M. Efinaconazole 10% nail solution: a new topical treatment with broad antifungal activity for onychomycosis monotherapy. J Cutan Med Surg. 2014 May-Jun;18(3):151-5. doi: 10.2310/7750.2013.13095. PMID: 24800702.
9: Pollak RA, Siu WJJ, Tatsumi Y, Pillai R. Efinaconazole Topical Solution, 10%: Factors Contributing to Onychomycosis Success. J Fungi (Basel). 2015 Jul 3;1(2):107-114. doi: 10.3390/jof1020107. PMID: 29376902; PMCID: PMC5753103.
10: Lipner SR, Scher RK. Efinaconazole 10% topical solution for the topical treatment of onychomycosis of the toenail. Expert Rev Clin Pharmacol. 2015;8(6):719-31. doi: 10.1586/17512433.2015.1083418. Epub 2015 Aug 31. PMID: 26325488.
11: Efinaconazole for Fungal Nail Infections: A Review of the Clinical Effectiveness, Cost-effectiveness, and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Jan 15. PMID: 26889524.
12: Gupta AK, Stec N, Summerbell RC, Shear NH, Piguet V, Tosti A, Piraccini BM. Onychomycosis: a review. J Eur Acad Dermatol Venereol. 2020 Sep;34(9):1972-1990. doi: 10.1111/jdv.16394. Epub 2020 Jun 5. PMID: 32239567.
13: Saunders J, Maki K, Koski R, Nybo SE. Tavaborole, Efinaconazole, and Luliconazole: Three New Antimycotic Agents for the Treatment of Dermatophytic Fungi. J Pharm Pract. 2017 Dec;30(6):621-630. doi: 10.1177/0897190016660487. Epub 2016 Aug 3. PMID: 27488125.
14: Gupta AK, Summerbell RC, Venkataraman M, Quinlan EM. Nondermatophyte mould onychomycosis. J Eur Acad Dermatol Venereol. 2021 Aug;35(8):1628-1641. doi: 10.1111/jdv.17240. Epub 2021 Apr 18. PMID: 33763903.
15: Falotico JM, Lipner SR. Updated Perspectives on the Diagnosis and Management of Onychomycosis. Clin Cosmet Investig Dermatol. 2022 Sep 15;15:1933-1957. doi: 10.2147/CCID.S362635. PMID: 36133401; PMCID: PMC9484770.
16: Patel T, Dhillon S. Efinaconazole: first global approval. Drugs. 2013 Nov;73(17):1977-83. doi: 10.1007/s40265-013-0152-x. PMID: 24249649.
17: Frazier WT, Santiago-Delgado ZM, Stupka KC 2nd. Onychomycosis: Rapid Evidence Review. Am Fam Physician. 2021 Oct 1;104(4):359-367. PMID: 34652111.
18: Gupta AK, Cernea M. How effective is efinaconazole in the management of onychomycosis? Expert Opin Pharmacother. 2016;17(4):611-8. doi: 10.1517/14656566.2016.1146687. Epub 2016 Feb 15. PMID: 26809447.
19: Pharmacoeconomic Review Report: Efinaconazole (Jublia): (Valeant Canada LP): Indication: For the topical treatment of mild-to-moderate onychomycosis (tinea unguium) of toenails without lunula involvement due to Trichophyton rubrum and Trichophyton mentagrophytes in immunocompetent adult patients [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Jun. PMID: 31287636.
20: Clinical Review Report: Efinaconazole (Jublia): (Valeant Canada LP): Indication: For the topical treatment of mild-to-moderate onychomycosis (tinea unguium) of toenails without lunula involvement due to Trichophyton rubrum and Trichophyton mentagrophytes in immunocompetent adult patients [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Jun. PMID: 31305972.
