| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
|
||
| Other Sizes |
| Targets |
Terbinafine HCl primarily targets squalene monooxygenase (squalene epoxidase), a key enzyme in the ergosterol biosynthesis pathway. It acts as a potent non-competitive inhibitor of this enzyme. In Candida, the inhibition constant (Ki) is 30 nM. By blocking squalene epoxidase, the compound prevents the conversion of squalene to 2,3-oxidosqualene, thereby depleting ergosterol, an essential component of fungal cell membranes.
|
|---|---|
| ln Vitro |
In vitro, terbinafine predominantly acts as a fungicidal agent against a variety of fungal diseases, such as filamentous, dimorphic, and dermatophytes. At the squalene epoxidation site, terbinafine selectively inhibits the formation of fungal ergosterol. The ultimate byproduct of the mechanism, ergosterol, is absent from treated fungal cells, which instead quickly accumulate the intermediate squalene [1].
Terbinafine HCl demonstrates potent antifungal activity against a broad range of dermatophytes and yeasts. It exhibits a Ki of 30 nM against Candida squalene epoxidase in cell-free assays. The compound also shows antibacterial activity against certain Gram-positive and Gram-negative bacteria. In addition, terbinafine inhibits proliferation of oral squamous cell carcinoma cells through inhibition of kinase suppressor of RAS 1 (KSR1). |
| ln Vivo |
Terbinafine has been shown to be particularly effective against experimental dermatophytosis both when applied topically and when taken orally. Skin temperature in guinea pigs afflicted with fungus decreased significantly during the fourth terbinafine therapy [2].
In vivo, terbinafine HCl is effective against various fungal infections. It is used topically and orally for the treatment of dermatophyte infections of the skin and nails. The drug is also effective against pityriasis versicolor, a fungal infection causing skin discoloration. Oral administration achieves therapeutic concentrations in the stratum corneum, hair, and nails due to its lipophilic nature and high tissue affinity. |
| Enzyme Assay |
The in vitro enzyme assay for terbinafine HCl typically involves measuring its inhibition of squalene epoxidase activity. The enzyme is incubated with radiolabeled squalene substrate and varying concentrations of the compound. The reaction product, 2,3-oxidosqualene, is quantified by chromatographic methods. The Ki value is determined from enzyme kinetic studies using Candida microsomal preparations. Terbinafine acts as a non-competitive inhibitor with a Ki of approximately 30 nM against the Candida enzyme.
|
| Cell Assay |
In vitro cell-based assays for terbinafine HCl use fungal cell cultures, typically Candida species or dermatophytes. Cells are cultured in appropriate growth media and exposed to serial dilutions of the compound. Antifungal activity is assessed by determining the minimum inhibitory concentration (MIC) using broth microdilution methods per CLSI guidelines. Cell proliferation is measured by optical density or colony counting after 24-48 hours of incubation. The compound's effect on ergosterol content can also be quantified by HPLC analysis of extracted lipids from treated cells.
|
| Animal Protocol |
In vivo animal models for terbinafine HCl include guinea pig models of dermatophytosis. Animals are infected with Trichophyton mentagrophytes on shaved skin, then treated with topical or oral terbinafine at various doses. Efficacy is evaluated by clinical scoring of skin lesions and mycological culture of skin samples. Pharmacodynamic parameters such as the effective dose for 50% cure (ED50) are calculated. Pharmacokinetic studies in rodents measure drug concentrations in plasma, skin, and nail tissues following oral or topical administration.
|
| ADME/Pharmacokinetics |
Terbinafine HCl is highly lipophilic with excellent oral bioavailability. Following oral administration, it is extensively distributed into tissues, particularly skin, hair, and nails, where it accumulates at fungicidal concentrations. The drug is metabolized in the liver by cytochrome P450 enzymes, primarily CYP2C9, CYP1A2, and CYP3A4, to inactive metabolites. The terminal elimination half-life is approximately 200-400 hours after multiple dosing due to slow release from tissues. Excretion occurs mainly via urine and feces as metabolites.
|
| Toxicity/Toxicokinetics |
The toxicity profile of terbinafine HCl includes gastrointestinal disturbances, headache, and skin reactions as common adverse effects. Hepatotoxicity is a rare but serious adverse event, requiring liver function monitoring during prolonged therapy. Taste disturbances, including loss of taste, have also been reported. At therapeutic doses, the drug is generally well-tolerated, but caution is advised in patients with pre-existing liver disease. Drug interactions may occur with CYP2D6 substrates due to mild inhibition of this enzyme.
|
| References | |
| Additional Infomation |
Terbinafine hydrochloride is a hydrochloride salt prepared by reacting terbinafine with an equimolar amount of hydrogen chloride. It is an EC 1.14.13.132 (squalene monooxygenase) inhibitor and a P450 inhibitor. It is a hydrochloride-based allylamine antifungal drug containing a terbinafine (1+) ligand. Terbinafine hydrochloride is a synthetic allylamine derivative with a structure similar to naftifine. Terbinafine hydrochloride blocks ergosterol biosynthesis by inhibiting squalene epoxidase (part of the fungal cell membrane sterol synthesis pathway). It is highly lipophilic and readily accumulates in the skin, nails, and adipose tissue. Terbinafine is effective against dermatophytes. (NCI04) A naphthalene derivative that inhibits fungal squalene epoxidase and is used to treat fungal infections of the skin and nails. See also: Terbinafine (broad spectrum).
Drug Indications Treatment of onychomycosis Treatment of onychomycosis Terbinafine HCl is approved by the FDA and EMA for the treatment of onychomycosis and dermatophyte skin infections. It is marketed as Lamisil and available in oral tablet and topical cream formulations. The recommended oral dose for onychomycosis is 250 mg daily for 6-12 weeks. The drug is also used off-label for other fungal infections. Its mechanism involves selective inhibition of fungal squalene epoxidase, with lower affinity for the mammalian enzyme, contributing to its favorable safety profile. |
| Molecular Formula |
C21H26CLN
|
|---|---|
| Molecular Weight |
327.8908
|
| Exact Mass |
327.175
|
| CAS # |
78628-80-5
|
| Related CAS # |
Terbinafine;91161-71-6;Terbinafine-d3 hydrochloride;1310012-15-7;Terbinafine lactate;335276-86-3
|
| PubChem CID |
5282481
|
| Appearance |
White to off-white solid powder
|
| Density |
1.007g/cm3
|
| Boiling Point |
417.9ºC at 760 mmHg
|
| Melting Point |
204-208°C
|
| Flash Point |
183.7ºC
|
| Index of Refraction |
1.586
|
| LogP |
5.679
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
1
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
23
|
| Complexity |
428
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)(C)C#C/C=C/CN(C)CC1=CC=CC2=CC=CC=C21.Cl
|
| InChi Key |
BWMISRWJRUSYEX-SZKNIZGXSA-N
|
| InChi Code |
InChI=1S/C21H25N.ClH/c1-21(2,3)15-8-5-9-16-22(4)17-19-13-10-12-18-11-6-7-14-20(18)19;/h5-7,9-14H,16-17H2,1-4H3;1H/b9-5+;
|
| Chemical Name |
(E)-N,6,6-trimethyl-N-(naphthalen-1-ylmethyl)hept-2-en-4-yn-1-amine;hydrochloride
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~60 mg/mL (~182.99 mM)
H2O : ~1 mg/mL (~3.05 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 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 (7.62 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 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 (7.62 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: 13.75 mg/mL (41.93 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0498 mL | 15.2490 mL | 30.4980 mL | |
| 5 mM | 0.6100 mL | 3.0498 mL | 6.0996 mL | |
| 10 mM | 0.3050 mL | 1.5249 mL | 3.0498 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
