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Purity: ≥98%
Liranaftate (formerly M-732; Piritetrate; Zefnart) is a thiocarbamate-based inhibitor of squalene epoxidase with fungicidal activities. It inhibits fungal squalene epoxidase, which is an enzyme that plays a key role in the synthesis of sterol, compouds essential for cell membrane integrity. By preventing ergosterol synthesis and causing accumulation of squalene, this agent increases cell membrane permeability, cell leakage and eventually cell lysis. Liranaftate showed excellent fungistatic activity against the conidia of T. rubrum. For each of these agents, the MIC after 14 days of contact was 0.009 g/ml. The liranaftate-induced decrease in the MCC occurred from 9 days onwards; MCC at 14 days was 0.039 g/ml. In time-kill studies, liranaftate showed the greatest decrease to a below detection limit in viable counts of T rubrum. The degree of killing of the strain by amorolfine was not greater than that seen by liranaftate, and little reduction of the viable counts by luliconazole and ketoconazole was observed irrespective of concentrations of the agents.
| Targets |
Fungal squalene epoxidase [1][2]
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| ln Vitro |
Liranaftate has outstanding antibacterial efficacy against T. rubrum conidia. The minimum inhibitory concentration (MIC) for each of these drugs was 0.009 g/ml during a 14-day exposure period. Day 9 saw the beginning of the lignate-induced decrease in MCC, which reached 0.039 g/ml on day 14 [1]. Liranate demonstrated the largest decrease in viable counts of Mucor rubrum below the detection limit in time-kill studies. No matter the drug concentration, luliconazole and ketoconazole exhibited no decrease in viable bacterial counts, and amorolfine did not kill strains more than liranate [2].
Antifungal activity against Trichophyton rubrum: Liranaftate showed fungicidal effect with minimum inhibitory concentration (MIC) of 0.0039-0.0156 μg/mL and minimum fungicidal concentration (MFC) of 0.0078-0.0313 μg/mL against clinical isolates of Trichophyton rubrum [1] - Antifungal activity against dermatophytes: Liranaftate exhibited potent fungicidal activity against Trichophyton mentagrophytes, Microsporum canis, and Epidermophyton floccosum, with MIC ranges of 0.0039-0.0156 μg/mL and MFC ranges of 0.0078-0.0313 μg/mL [2] - Inhibition of IL-8 production in human keratinocytes: Liranaftate (0.1-10 μg/mL) dose-dependently suppressed IL-8 production induced by Trichophyton rubrum extract (10 μg/mL) in normal human keratinocytes; 10 μg/mL Liranaftate reduced IL-8 levels by ~72% compared to stimulated control (ELISA assay) [4] - Liranaftate (0.01-1 μg/mL) inhibited the growth of Trichophyton rubrum mycelium in vitro, with complete growth inhibition at 0.1 μg/mL after 72 hours of incubation [1] |
| ln Vivo |
Suppression of croton oil-induced ear edema in mice: Topical application of Liranaftate (0.1%, 0.3%, 1%) dose-dependently inhibited ear edema; 1% Liranaftate reduced edema by ~65% compared to vehicle control [3]
- Inhibition of carrageenan-induced paw edema in mice: Intraperitoneal administration of Liranaftate (10 mg/kg, 30 mg/kg) inhibited paw edema at 4 hours post-carrageenan injection; 30 mg/kg dose showed ~58% inhibition [3] - Suppression of Trichophyton rubrum-induced skin inflammation in mice: Topical Liranaftate (0.3%) twice daily for 7 days reduced skin redness, scaling, and thickness by ~60% compared to untreated infected mice [2] |
| Cell Assay |
Normal human keratinocytes were cultured in appropriate medium (37°C, 5% CO2) and seeded in 24-well plates (5×104 cells/well) overnight. Cells were pre-treated with Liranaftate (0.1-10 μg/mL) for 1 hour, then stimulated with Trichophyton rubrum extract (10 μg/mL) for 24 hours. Culture supernatants were collected, and IL-8 concentration was measured by ELISA [4]
- Trichophyton rubrum was cultured on Sabouraud dextrose agar at 28°C for 7 days. Fungal suspension (1×105 CFU/mL) was mixed with serial dilutions of Liranaftate (0.001-0.1 μg/mL) in RPMI 1640 medium, incubated at 28°C for 48 hours. MIC was determined as the lowest concentration inhibiting visible fungal growth; MFC was determined by subculturing on drug-free agar and counting viable colonies [1] |
| Animal Protocol |
Croton oil-induced ear edema model: Male ICR mice (6-8 weeks old) were randomly divided into vehicle control and Liranaftate treatment groups (n=6/group). Croton oil (20 μL) was applied to the right ear to induce edema. Liranaftate (0.1%, 0.3%, 1% in appropriate vehicle) was topically applied to the right ear 30 minutes before and 1 hour after croton oil application. Ear thickness was measured 4 hours after edema induction [3]
- Carrageenan-induced paw edema model: Male ICR mice were intraperitoneally administered Liranaftate (10 mg/kg, 30 mg/kg) or vehicle 30 minutes before subcutaneous injection of carrageenan (0.1 mL, 1% w/v) into the right hind paw. Paw volume was measured using a plethysmometer at 1, 2, 4, and 6 hours post-carrageenan injection [3] - Trichophyton rubrum skin infection model: Male BALB/c mice were inoculated with Trichophyton rubrum conidia (1×106 CFU) on shaved dorsal skin. Liranaftate (0.3% in vehicle) was topically applied twice daily for 7 days. Skin inflammation was evaluated by redness score, scaling score, and skin thickness measurement [2] |
| References |
[1]. Oku, Y., et al., [Fungicidal activity of liranaftate against Trichophyton rubrum]. Nihon Ishinkin Gakkai Zasshi, 2002. 43(3): p. 181-7.
[2]. Oku, Y., N. Takahashi, and K. Yokoyama, [Fungicidal activity of liranaftate against dermatophytes]. Nihon Ishinkin Gakkai Zasshi, 2009. 50(1): p. 9-13. [3]. Maruyama N, et, al. [Suppression of experimental inflammation by anti-fungal agent liranaftate in mice]. Nihon Ishinkin Gakkai Zasshi. 2010;51(1):7-11. [4]. Kobayashi M, et, al. [Anti-fungal drug liranaftate suppresses fungal element-promoted production of IL-8 in normal human keratinocytes]. Nihon Ishinkin Gakkai Zasshi. 2008;49(4):319-22. |
| Additional Infomation |
Liranaftate ester belongs to the tetrahydronaphthalene class of compounds. It is a thiocarbamate and squalene epoxidase inhibitor with antifungal activity. Liranafyl ester inhibits fungal squalene epoxidase, an enzyme that plays a crucial role in sterol synthesis, which is essential for cell membrane integrity. By inhibiting ergosterol synthesis and leading to squalene accumulation, the drug increases cell membrane permeability, causing cell leakage and ultimately cell lysis.
Liranazate (Piritetrate; M-732) is a synthetic antifungal drug belonging to the squalene epoxidase inhibitor class[1][2] - Its antifungal mechanism involves inhibiting fungal squalene epoxidase, thereby blocking the biosynthesis of ergosterol, which is essential for the integrity of fungal cell membranes[1][2] - In addition to its antifungal activity, liranazate also exerts an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokine (IL-8) in keratinocytes, which helps treat fungal skin inflammation[3][4] - liranazate is mainly used for the topical treatment of dermatophyte infections (e.g., tinea corporis, tinea). Due to its potent activity against Trichophyton, Microsporum, and Epidermophyton, it is also used to treat tinea cruris and tinea pedis[1][2]. |
| Molecular Formula |
C18H20N2O2S
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| Molecular Weight |
328.43
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| Exact Mass |
328.124
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| Elemental Analysis |
C, 62.77; H, 5.85; N, 8.13; O, 13.94; S, 9.31
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| CAS # |
88678-31-3
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| Related CAS # |
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| PubChem CID |
3936
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| Appearance |
Solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
462.5±55.0 °C at 760 mmHg
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| Melting Point |
98.5-99.5ºC
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| Flash Point |
233.5±31.5 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.642
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
407
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S=C(N(C)C1C=CC=C(OC)N=1)OC1C=C2CCCCC2=CC=1
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| InChi Key |
GTLOCRWOJSGVDM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H20N2O3S/c1-22-17-9-5-8-16(19-17)20(24-2)18(21)23-15-11-10-13-6-3-4-7-14(13)12-15/h5,8-12H,3-4,6-7H2,1-2H3
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| Chemical Name |
O-(5,6,7,8,-Tetrahydro-2-naphthyl) 6-methoxy-N-methylthio-2-pyridinecarbamate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 25~100 mg/mL ( 76.11~304.48 mM )
H2O < 0.1 mg/mL tert-Butanol : ~11 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.61 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (7.61 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: 2.5 mg/mL (7.61 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0448 mL | 15.2239 mL | 30.4479 mL | |
| 5 mM | 0.6090 mL | 3.0448 mL | 6.0896 mL | |
| 10 mM | 0.3045 mL | 1.5224 mL | 3.0448 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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