API Liranaftate

Liranaftate More Info

Overview

Liranaftate (also known as Piritetrate or M-732) is a thiocarbamate antifungal agent with potent activity against dermatophytes. Developed by Torii Pharmaceutical Company in Japan, it was launched in August 2000 as a next-generation antifungal drug for the treatment of superficial fungal infections.

Chemical Properties

Liranaftate has the chemical name N-[(6-methoxy-2-pyridyl)-N-methylcarbamoylthio]-2-naphthyl ester (5,6,7,8-tetrahydronaphthalene-2-yl). Its molecular formula is C₁₈H₂₀N₂O₂S with a molecular weight of 328.43 Da. The CAS Number is 88678-31-3. This compound typically has a purity of ≥98% to 99.98%, appears as white or off-white crystalline powder, has a melting point between 96.0°C and 100.0°C, and is soluble in DMSO at 9 mg/mL (27.4 mM).

Mechanism of Action

Liranaftate is a potent squalene epoxidase inhibitor that works through several steps. First, it inhibits squalene epoxidase, which is a key enzyme in fungal ergosterol biosynthesis. This prevents the conversion of squalene to lanosterol, blocking sterol synthesis. The drug causes accumulation of squalene within the fungal cell, which increases cell membrane permeability and leads to cellular leakage. Ultimately, this causes cell rupture and fungal cell death.

Pharmacological Properties

Antifungal Activity

Liranaftate shows excellent fungistatic activity against Trichophyton rubrum conidia. It is effective against tinea corporis, tinea cruris, and tinea pedis (athlete's foot). The drug has high efficacy with sustained therapeutic effects and requires less frequent dosing compared to other antifungal agents.

Anti-inflammatory Activity

The compound suppresses IL-8 production induced by fungal components such as β-glucan and trichophytin. It reduces neutrophil infiltration in skin tissue and inhibits neutrophil invasion into the epidermis. Liranaftate also demonstrates anti-edema effects in experimental models.

Safety Profile

Clinical trials have confirmed a high safety profile with minimal side effects reported. The drug is well-tolerated in both in vitro and in vivo studies.

Research Applications

Liranaftate is widely used in scientific research for fungal pathogenesis studies, particularly for investigating biochemical pathways involved in ergosterol biosynthesis. It helps researchers understand how fungi develop antifungal drug resistance and explore the molecular basis of thiocarbamate enzyme inhibition. The compound is also useful for antifungal drug development, identifying new targets for antifungal agents, and studying the role of neutrophils and IL-8 in fungal skin infections.

In Vitro and In Vivo Activity

In vitro studies show that Liranaftate effectively suppresses IL-8 production in keratinocytes when combined with β-glucan or trichophytin. It exhibits dose-dependent inhibition of fungal conidia and maintains activity in antifungal challenge assays.

In vivo studies demonstrate that topical application at 1-4% concentration suppresses ear thickness increase in PMA-induced inflammation models. The drug reduces myeloperoxidase (MPO) activity, which is a marker of neutrophil accumulation, and shows anti-inflammatory effects in mouse ear edema models.

Product Specifications

Liranaftate is available in powder form with sizes ranging from 5mg to 200mg. DMSO solutions come in 1mL x 10mM format. Custom solutions are also available upon request.

Storage Conditions

Powder should be stored at -20°C to -25°C with a shelf life of 3 years. DMSO solutions should be stored at -80°C with a shelf life of 1 year. After solvent addition, solutions should be kept at -20°C and used within 1 month.

Preparation Instructions

For a 10mM DMSO solution, dissolve 32.84 mg of Liranaftate in 10 mL of DMSO. Ultrasonic treatment is recommended for complete dissolution. Filter sterilization may be required for cell culture applications.

Important Notice

This product is intended for research use only. It should NOT be used for clinical diagnosis, treatment, or veterinary applications unless properly approved for such purposes.

Applications

The main applications include dermatological research, antifungal mechanism studies, inflammation pathway investigations, drug development screening, and enzyme inhibition studies.

Available Sources

Liranaftate is commercially available from several scientific suppliers including TargetMol, MedChemExpress (MCE), Santa Cruz Biotechnology (SCBT), Yeasen Biotechnology, BioCrick, and BioMart.

Proprietary Preparations

Available in Japan under the brand name Zefnart as a 2% cream or solution for topical application.

Patent Information

The original compound preparation patent is GB2124617 from 1982. The compound is not patented in China, allowing for local development without patent restrictions.