| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Amorolfine HCl (Ro 14-4767/002), a topically administered drug, is a potent and broad-spectrum antifungal agent with fungicidal effects against most fungi, dermatophytes and yeasts. Amorolfine blocks ergosterol biosynthesis by interfering with delta 14 reduction and the delta 7-8 isomerisation. Amorolfine is an antifungal showing activity against fungi pathogenic to plants, animals and humans. At 0.2, 2 and 5 micrograms/ml amorolfine did not have any significant inhibitory or enhancing effect on phagocytosis whether following simultaneous addition of blastospores and drug to the neutrophils, prior treatment of neutrophils for 2 h before addition of blastospores or prior treatment of blastospores for 2 h.
| Targets |
Fungal lanosterol 14α-demethylase [1, 4]
- Fungal ergosterol biosynthesis pathway [1, 3, 4] |
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| ln Vitro |
Amorolfine hydrochloride has both fungistatic and fungicidal properties, and its primary mode of action is to inhibit the biosynthesis of ergosterol, a component of the fungal cell membrane.
Amorolfine hydrochloride (0–128 mg/l) for 2–7 days exhibits antifungal activity against pathogenic yeasts, dimorphic fungi, dematiaceous fungi, and Dermatophyte fungi.With 90% killing corresponding concentrations of 3, 3, 10, and 100 mg/L for Trichophyton mentagrophytes, C. albicans, Histoplasma capsulatum, and Cryptococcus neoformans, respectively, amorolfine hydrochloride exhibits anti-fungal activity[1].
Exhibited broad-spectrum antifungal activity against dermatophytes, yeasts, and molds, with minimum inhibitory concentrations (MIC) ranging from 0.03 to 4 μg/mL [4] - Potently inhibited growth of Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum (MIC = 0.03-0.25 μg/mL), key pathogens of dermatophytosis [4] - Inhibited Candida albicans (MIC = 0.5-2 μg/mL) and Malassezia furfur (MIC = 0.125-0.5 μg/mL), common yeasts causing skin infections [1, 4] - Disrupted fungal cell membrane integrity by inhibiting ergosterol synthesis: 1 μg/mL Amorolfine HCl (Ro 14-4767/002) reduced ergosterol content in T. rubrum by ~70% after 24-hour incubation, leading to increased membrane permeability [1, 4] - Showed fungicidal activity at concentrations ≥2×MIC: 2 μg/mL killed 99% of C. albicans cells within 48 hours [4] |
| ln Vivo |
In rats with vaginal candidiasis, amorolfine hydrochloride (0.01%–1%; intravaginal application; twice daily for three days) exhibits anti-fungal activity[1].
In a guinea pig Trichophyton mentagrophytes-induced tinea corporis model, topical application of 0.25% Amorolfine HCl (Ro 14-4767/002) cream once daily for 14 days resulted in ~90% cure rate, with complete clearance of fungal hyphae in skin scrapings [3, 4] - In a clinical trial of 120 patients with onychomycosis, topical application of 5% Amorolfine HCl (Ro 14-4767/002) nail lacquer once weekly for 6 months achieved ~65% mycological cure (negative fungal culture) and ~50% clinical cure (nail appearance improvement) [2] - Reduced nail plate fungal load by ~80% in patients with distal subungual onychomycosis after 3 months of treatment [2] - Inhibited fungal invasion of nail matrix in animal models: 1% concentration prevented T. rubrum-induced nail discoloration and thickening by ~75% [3] |
| Enzyme Assay |
Fungal ergosterol synthesis inhibition assay: T. rubrum cells were cultured in Sabouraud dextrose broth with various concentrations of Amorolfine HCl (Ro 14-4767/002) (0.01-4 μg/mL) for 48 hours. Cells were harvested, and total sterols were extracted. Ergosterol content was quantified by high-performance liquid chromatography (HPLC) with UV detection, and inhibition rate was calculated relative to untreated control [4]
- Lanosterol 14α-demethylase activity assay: Recombinant fungal lanosterol 14α-demethylase was incubated with lanosterol (substrate), NADPH, and Amorolfine HCl (Ro 14-4767/002) (0.01-10 μg/mL) in reaction buffer. After incubation at 30°C for 60 minutes, the reaction was stopped by adding methanol. The formation of 4,4-dimethylcholesta-8,14,24-trien-3β-ol (reaction product) was detected by HPLC, and enzyme inhibition rate was determined [1] |
| Cell Assay |
Microdilution antifungal susceptibility assay: Fungal strains (T. rubrum, C. albicans, M. furfur) were suspended in RPMI 1640 medium to a concentration of 1×104 CFU/mL. Serial dilutions of Amorolfine HCl (Ro 14-4767/002) (0.001-16 μg/mL) were added to 96-well plates, followed by fungal suspension. Plates were incubated at 35°C for 48-72 hours. MIC was defined as the lowest concentration inhibiting visible fungal growth [4]
- Fungal cell membrane permeability assay: T. rubrum cells were treated with Amorolfine HCl (Ro 14-4767/002) (1-4 μg/mL) for 24 hours. Cells were stained with propidium iodide (PI), and fluorescence intensity was measured by flow cytometry to assess membrane integrity (PI penetrates damaged membranes) [1] |
| Animal Protocol |
Animal Model: Rats (vaginal candidiasis)[1]
Dosage: 0.01%-1% Administration: Intravaginal application; twice daily for 3 days Result: produced a dose-dependent log reduction in the number of cells; a 1% concentration totally removed C. albicans from the vagina. Guinea pig tinea corporis model: Male guinea pigs (300-350 g) were shaved on the back and inoculated with T. mentagrophytes conidial suspension (1×106 CFU/mL) by scarification. After 7 days (establishment of infection), Amorolfine HCl (Ro 14-4767/002) was formulated as 0.25% cream and applied topically to the infected area (0.1 g/cm2) once daily for 14 days. Control group received placebo cream. Skin scrapings were collected at day 14 for fungal culture and histopathological examination (PAS staining for hyphae) [3, 4] |
| ADME/Pharmacokinetics |
Topical application in humans: systemic absorption is minimal; after 6 months of nail polish use, the plasma concentration of amorolfine hydrochloride (Ro 14-4767/002) was below the detection limit (<0.5 ng/mL) [1, 2] - Skin penetration: after topical application of the cream, the drug accumulates in the epidermis and dermis (concentration > MIC of most dermatophytes), with minimal transdermal absorption [1] - Nail penetration: 5% nail polish slowly penetrates the nail plate, reaching a steady-state concentration (~2 μg/g) in nail tissue after 4 weeks of weekly application [2] - Due to low systemic absorption, the plasma half-life (t1/2) cannot be determined; metabolism and excretion in urine/feces are negligible [1]
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| Toxicity/Toxicokinetics |
Acute toxicity: Oral LD50 in rats > 5000 mg/kg; Dermal LD50 in rabbits > 2000 mg/kg [1]
- Subchronic toxicity: No skin irritation, allergic reactions, or changes in liver and kidney function were observed in rabbits after daily dermal application of 1% cream for 28 days [1, 3] - Local toxicity in humans: Approximately 5% of patients reported mild and transient skin reactions (erythema, pruritus, dryness); no serious local or systemic toxicity was observed [2, 3] |
| References | |
| Additional Infomation |
Amorolfine hydrochloride is a hydrochloride salt formed by the reaction of equimolar amounts of hydrogen chloride and amorolfine. It is an inhibitor of squalene monooxygenase, δ¹⁴ reductase, and D₇-D₈ isomerase, and also an antifungal agent used topically to treat fungal onychomycosis and skin infections. It can act as an inhibitor of EC 1.14.13.132 (squalene monooxygenase), EC 5.3.3.5 (cholesterol δ-isomerase), and EC 1.3.1.70 (δ¹⁴-sterol reductase). It is a hydrochloride salt and also a morpholine antifungal drug. It contains amorolfine (1+). Amorolfine hydrochloride is the hydrochloride form of the morpholine antifungal agent amorolfine. Amorolfine inhibits δ-14-reductase and δ-7,8-isomerase, thereby consuming ergosterol, leading to the accumulation of isostosterol in the fungal cell membrane.
Amorolfen hydrochloride (Ro 14-4767/002) is a synthetic broad-spectrum antifungal drug belonging to the morpholine class [1, 3, 4]. Its core mechanism of action is the inhibition of fungal lanosterol 14α-demethylase (a key enzyme in ergosterol biosynthesis), leading to the depletion of ergosterol (essential for fungal cell membrane integrity) and the accumulation of toxic sterol intermediates [1, 4]. Clinically, it is used to treat superficial fungal infections, including onychomycosis (nail fungus), tinea corporis, tinea cruris, and tinea versicolor. [1, 2, 3] Due to minimal systemic absorption, it can be formulated into topical preparations (nail polish, cream, solution) to ensure high local drug concentrations and low systemic side effects. [1, 2] In rare cases, cross-resistance to azole antifungal drugs may occur due to target enzyme mutations, but it remains active against most azole-sensitive fungal strains and some azole-resistant fungal strains. [4] |
| Molecular Formula |
C21H35NO.HCL
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| Molecular Weight |
353.97
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| Exact Mass |
353.248
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| Elemental Analysis |
C, 71.26; H, 10.25; Cl, 10.01; N, 3.96; O, 4.52
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| CAS # |
78613-38-4
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| Related CAS # |
67467-83-8;78613-35-1;78613-38-4 (HCl);
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| PubChem CID |
54259
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| Appearance |
White to off-white solid powder
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| Density |
1.234
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| Boiling Point |
78-82°C (9 Torr)
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| LogP |
5.401
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
24
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| Complexity |
336
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| Defined Atom Stereocenter Count |
2
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| SMILES |
Cl[H].O1[C@]([H])(C([H])([H])[H])C([H])([H])N(C([H])([H])[C@]1([H])C([H])([H])[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])[H]
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| InChi Key |
XZKWIPVTHGWDCF-KUZYQSSXSA-N
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| InChi Code |
InChI=1S/C21H35NO.ClH/c1-7-21(5,6)20-10-8-19(9-11-20)12-16(2)13-22-14-17(3)23-18(4)15-22;/h8-11,16-18H,7,12-15H2,1-6H3;1H/t16?,17-,18+;
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| Chemical Name |
(2R,6S)-2,6-dimethyl-4-(2-methyl-3-(4-(tert-pentyl)phenyl)propyl)morpholine hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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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) |
Ethanol : ~71 mg/mL
DMSO : 12.5~23 mg/mL ( 35.31 ~64.97 mM ) Water : 2~3.33 mg/mL(~9.41 mM ) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.53 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 12.5 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: ≥ 1.25 mg/mL (3.53 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 12.5 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: ≥ 1.25 mg/mL (3.53 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: ≥ 1.25 mg/mL (3.53 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8251 mL | 14.1255 mL | 28.2510 mL | |
| 5 mM | 0.5650 mL | 2.8251 mL | 5.6502 mL | |
| 10 mM | 0.2825 mL | 1.4125 mL | 2.8251 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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