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.

Physicochemical Properties

Molecular Formula	C18H20N2O2S
Molecular Weight	328.43
Exact Mass	328.124
Elemental Analysis	C, 62.77; H, 5.85; N, 8.13; O, 13.94; S, 9.31
CAS #	88678-31-3
Related CAS #	88678-31-3
PubChem CID	3936
Appearance	Solid powder
Density	1.2±0.1 g/cm3
Boiling Point	462.5±55.0 °C at 760 mmHg
Melting Point	98.5-99.5ºC
Flash Point	233.5±31.5 °C
Vapour Pressure	0.0±1.1 mmHg at 25°C
Index of Refraction	1.642
LogP	5.2
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	23
Complexity	407
Defined Atom Stereocenter Count	0
SMILES	S=C(N(C)C1C=CC=C(OC)N=1)OC1C=C2CCCCC2=CC=1
InChi Key	GTLOCRWOJSGVDM-UHFFFAOYSA-N
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
Chemical Name	O-(5,6,7,8,-Tetrahydro-2-naphthyl) 6-methoxy-N-methylthio-2-pyridinecarbamate
Synonyms	M732; M 732; M-732;Piritetrate;Zefnart
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

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].
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 is a member of tetralins. Liranaftate is a thiocarbamate and squalene epoxidase inhibitor with antifungal activity. Liranaftate inhibits fungal squalene epoxidase, an enzyme that plays a key role in the synthesis of sterol which is 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.

Solubility Data

Solubility (In Vitro)

DMSO : 25~100 mg/mL ( 76.11~304.48 mM ) H2O < 0.1 mg/mL tert-Butanol : ~11 mg/mL

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. 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. 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 corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: 2.5 mg/mL (7.61 mM)  (Please use freshly prepared in vivo formulations for optimal results.)

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.