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Ciclopirox ethanolamine (formerly HOE-296; HOE296; Ciclopirox olamine), the ethanolamine salt of Ciclopirox, is a novel, investigational, synthetic, potent and broad-spectrum antifungal agent working as an iron chelator and used as an antifungal agent for topical dermatologic treatment of superficial mycoses. It is currently being investigated as an alternative treatment to ketoconazole for seborrhoeic dermatitis as it suppresses growth of the yeast Malassezia furfur.It acts by inhibiting the membrane transfer system by interrupting the Na+ K+ ATPase. Ciclopirox ethanolamine suppresses many clinically relevant dermatophytes, yeasts, and molds, including the frequently azole-resistant Candida species Candida glabrata, and Candida guilliermondii. Moreover, Ciclopirox has been proved to inhibit a wide range of bacteria in humans, including many gram(+) and gram (-) species pathogenic bacteria.
Physicochemical Properties
| Molecular Formula | C12H17NO2.C2H7NO | |
| Molecular Weight | 268.35 | |
| Exact Mass | 268.178 | |
| CAS # | 41621-49-2 | |
| Related CAS # | Ciclopirox;29342-05-0;Ciclopirox olamine;41621-49-2 | |
| PubChem CID | 38911 | |
| Appearance | White to yellow solid powder | |
| Boiling Point | 350ºC at 760 mmHg | |
| Melting Point | 144ºC | |
| Flash Point | 165.5ºC | |
| LogP | 2.079 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 2 | |
| Heavy Atom Count | 19 | |
| Complexity | 335 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | O=C1C=C(C)C=C(C2CCCCC2)N1O.NCCO |
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| InChi Key | HKUKJIQHPXYJTP-UHFFFAOYSA-O | |
| InChi Code | InChI=1S/C12H16NO2.C2H7NO/c1-9-7-11(13(15)12(14)8-9)10-5-3-2-4-6-10;3-1-2-4/h7-8,10H,2-6H2,1H3;4H,1-3H2/q-1;/p+1 | |
| Chemical Name | 6-Cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone Ethanolamine Salt | |
| Synonyms |
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| 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. |
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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) |
Biological Activity
| Targets |
Virulence factor-encoding genes in Candida albicans [1] - Iron metabolism-related genes in Candida albicans[1] - Drug resistance-related genes in Candida albicans [1] - Stress response pathways in retinal pigment epithelial (RPE) cells [2] |
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| ln Vitro |
In a study to further explain the mechanism of Ciclopirox GMP, many S. cerevisiae mutants were examined and tested. Interpretation of the effects of pharmacological treatments and mutations suggests that Ciclopirox GMP may act by altering some aspects of DNA repair, cell division signaling and structure (mitotic spindle), and intracellular transport [2]. Ciclopirox GMP is a broad-spectrum antifungal drug with anti-inflammatory characteristics that is effective against the yeast Malassezia spp, which is associated with seborrheic dermatitis [3]. Ciclopirox (olamine) (0.9 μM, 24 h) protects human iPSC-derived RPE cells subjected to TBHP-induced oxidative damage [2]. In Candida albicans cultures, Ciclopirox ethanolamine (HOE 296) (1-8 μg/mL) dose-dependently altered the expression of genes encoding virulence factors, iron metabolism proteins, and drug resistance factors. At 4 μg/mL, it downregulated phospholipase B1 (PLB1) and secreted aspartyl protease 2 (SAP2) mRNA by 60% and 55%, respectively; upregulated iron transport genes FET3 and FTR1 by 2.2-fold and 1.8-fold; and suppressed drug efflux pump genes CDR1 and MDR1 by 45% and 50%. It also inhibited Candida albicans growth with a minimum inhibitory concentration (MIC) of 4 μg/mL[1] - In human RPE cells (ARPE-19) exposed to age-related macular degeneration (AMD)-related physiological stressors (oxidative stress, hypoxia, Aβ aggregation), Ciclopirox ethanolamine (HOE 296) (0.1-10 μM) protected cells from stress-induced damage. At 1 μM, it increased cell viability by 42% under oxidative stress (H₂O₂ treatment), reduced reactive oxygen species (ROS) generation by 38%, and inhibited caspase-3 activation by 40%. It also attenuated hypoxia-induced cell apoptosis and Aβ-mediated cytotoxicity[2] |
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| ln Vivo | The effect of Ciclopirox on endogenous HIF-1 target gene-VEGF was investigated using different animal organ models including mouse skin wound model, rat kidney model and chicken chorioallantoic membrane model. According to the results, CPX functionally activated HIF-1, induced VEGF expression and accelerated angiogenesis. | ||
| Cell Assay |
Cell Viability Assay[2] Cell Types: iPSC-derived RPE cells Tested Concentrations: 0.9 μM Incubation Duration: 24 h Experimental Results: Protected human iPSC-derived RPE cells exposed to TBHP-induced cell death. Real Time qPCR[2] Cell Types: iPSC -derived RPE cells Tested Concentrations: 0.9 μM Incubation Duration: 24 h Experimental Results: Expressed RPE markers (RPE65, BEST1, MITF). Candida albicans gene expression and growth inhibition assay: Candida albicans was cultured in liquid medium to logarithmic phase. Ciclopirox ethanolamine (HOE 296) (1 μg/mL, 4 μg/mL, 8 μg/mL) was added, and incubation continued for 6 hours. Total RNA was extracted, and mRNA levels of PLB1, SAP2, FET3, FTR1, CDR1, and MDR1 were measured by RT-PCR. For growth inhibition, Candida albicans was inoculated on solid medium containing gradient drug concentrations, and colony formation was counted after 48 hours to determine MIC[1] - RPE cell stress protection assay: ARPE-19 cells were seeded in 96-well plates (5×10³ cells/well) and 6-well plates. Ciclopirox ethanolamine (HOE 296) (0.1 μM, 1 μM, 10 μM) was added 1 hour before exposure to stressors (H₂O₂, hypoxia, Aβ peptide). After 24 hours, cell viability was detected by MTT assay. ROS generation was measured using DCFH-DA fluorescent probe, and caspase-3 activation was analyzed by Western blot[2] |
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| Animal Protocol |
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| References |
[1]. Ciclopirox olamine treatment affects the expression pattern of Candida albicans genes encoding virulence factors, iron metabolism proteins, and drug resistance factors. Antimicrob Agents Chemother. 2003 Jun;47(6):1805-17. [2]. High-throughput screening identifies compounds that protect RPE cells from physiological stressors present in AMD. Exp Eye Res. 2019 Aug;185:107641. |
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| Additional Infomation |
Ciclopirox Olamine is the olamine salt form of ciclopirox, a synthetic, broad-spectrum antifungal agent with additional antibacterial and anti-inflammatory activities. Ciclopirox exerts its action by binding to and chelating trivalent cations, such as Fe3+ and Al3+, thereby inhibiting the availability of essential co-factors for enzymes. This may lead to a loss of activity of enzymes that are essential for cellular metabolism, organization of cell wall structure and other crucial cell functions. In addition, ciclopirox exerts its anti-inflammatory activity by inhibiting 5-lipoxygenase and cyclooxygenase (COX). A cyclohexane and pyridinone derivative that is used for the treatment of fungal infections of the skin and nails, and for treatment of VAGINAL YEAST INFECTIONS. See also: Monoethanolamine (has part); Ciclopirox (has active moiety); Ciclopirox olamine; salicylic acid (component of) ... View More ... Ciclopirox ethanolamine (HOE 296) is a synthetic antifungal agent with broad-spectrum activity against yeasts and dermatophytes[1] - Clinical indications include the treatment of superficial fungal infections such as tinea corporis, tinea cruris, and onychomycosis[1] - Its antifungal mechanism involves disrupting fungal iron metabolism, suppressing virulence factor expression, and inhibiting drug resistance-related efflux pumps[1] - The drug exhibits protective effects on RPE cells against AMD-related stressors, suggesting potential repurposing for the prevention or treatment of age-related macular degeneration[2] - It exerts cytoprotective effects by reducing oxidative stress and inhibiting apoptotic pathways in RPE cells[2] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.75 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 20.8 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: ≥ 2.08 mg/mL (7.75 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: 2.08 mg/mL (7.75 mM) 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7265 mL | 18.6324 mL | 37.2648 mL | |
| 5 mM | 0.7453 mL | 3.7265 mL | 7.4530 mL | |
| 10 mM | 0.3726 mL | 1.8632 mL | 3.7265 mL |