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Ciclopirox olamine

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Chemical Structure| 41621-49-2 同义名 : 环吡酮乙醇胺盐;环吡司胺 ;Ciclopirox ethanolamine;HOE 296
CAS号 : 41621-49-2
货号 : A144214
分子式 : C14H24N2O3
纯度 : 99%
分子量 : 268.352
MDL号 : MFCD00078997
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(93.16 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • ATPase
描述 Transcription factor hypoxia inducible factor-1 (HIF-1) is a master switch under hypoxia that upregulates the expression of multiple angiogenic proteins including stromal derived factor (SDF)-1, placental growth factor (PlGF), endothelin-1, VEGF and its receptor VEGFR-1. HIF-1 consists of a HIF-1α and a HIF-1β subunit. Ciclopirox and its olamine salt are family members of hydroxypyridone, which is a prolyl hydroxylase inhibitor and can stabilize HIF-1α predominantly in fibroblasts induced capillary sprouting in endothelial cells to increase angiogenesis[6]. Moreover, ciclopirox is a potential drug for HBV. In a vitro study, HMSCs were stimulated with ciclopirox at dose of 10 μM for 24 h to perform subsequent gene expression analysis, suggesting that decrease of HIF-1α expression on gene level, whereas VEGF expression was upregulated by ciclopirox[7]. In another vitro assay, a kind of truncated HBV core protein, cp149, was incubated with 0.1 - 10 μM ciclopirox and an anti-HBV core antibody was added for immunoblot analysis. The result showed that IC50 value of ciclopirox was 445 ± 17 nM,, which indicated that ciclopirox potently affected intracellular HBV capsid assembly. In a vivo study, endothelial cells were cultured to observe sprouts of fibroblasts and only a few longer sprouts were observed. However, when ciclopirox at dose of 0.4 mM were introduced, an increase of sprout length ensued with the formation of a basal network and formation of anastomoses, indicating that ciclopirox induced secretion of VEGF[6]. In another study, human liver-chimeric uPA/SCID mice were injected intravenously with HBV virion (5 × 107 copies per mouse), and after 6 weeks the mice were treated daily with ciclopirox at dose of 5 mg/kg daily for 5 weeks. The data indicated that ciclopirox had lowered serum HBV DNA, HBeAg and serum ALT levels significantly. Furthermore, ciclopirox also significantly reduced HBV core protein levels in the liver. These evidences proved that ciclopirox is an effective HBV capsid assembly inhibitor[8].
作用机制 Hydrophobic residues L19, F23, F24, P25, Y118, F122, and W102, with extensive van der Waals interactions between ciclopirox and these residues form a binding pocket[9]. Ciclopirox Olamine is an olamine form of ciclopiro. And ciclopirox can mimic the effect of bipyridine, a well-known iron chelator and also an antifungal agent, upregulating the expression of the high-affinity iron permease gene FTR1 and the low-affinity iron permease gene FTR2, which are essential for iron metabolism[10].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.73mL

0.75mL

0.37mL

18.63mL

3.73mL

1.86mL

37.26mL

7.45mL

3.73mL
参考文献

[1]Zarember KA, Cruz AR, et al. Antifungal activities of natural and synthetic iron chelators alone and in combination with azole and polyene antibiotics against Aspergillus fumigatus. Antimicrob Agents Chemother. 2009 Jun;53(6):2654-6.

[2]Niewerth M, Kunze D, et al. 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.

[3]Bernier KM, Morrison LA, et al. Antifungal drug ciclopirox olamine reduces HSV-1 replication and disease in mice. Antiviral Res. 2018 Aug;156:102-106.

[4]Mihailidou C, Papakotoulas P, et al. Superior efficacy of the antifungal agent ciclopirox olamine over gemcitabine in pancreatic cancer models. Oncotarget. 2017 Dec 8;9(12):10360-10374.

[5]Weir SJ, Wood R, et al. Preclinical Pharmacokinetics of Fosciclopirox, a Novel Treatment of Urothelial Cancers, in Rats and Dogs. J Pharmacol Exp Ther. 2019 Aug;370(2):148-159.

[6]Lim SH, Kim C, Aref AR, Kamm RD, Raghunath M. Complementary effects of ciclopirox olamine, a prolyl hydroxylase inhibitor and sphingosine 1-phosphate on fibroblasts and endothelial cells in driving capillary sprouting. Integr Biol (Camb). 2013 Dec;5(12):1474-84.

[7]Kremer A, Wußmann M, Herrmann M, Raghunath M, Walles H. Ciclopirox olamine promotes the angiogenic response of endothelial cells and mesenchymal stem cells. Clin Hemorheol Microcirc. 2019;73(2):317-328.

[8]Kang JA, Kim S, Park M, Park HJ, Kim JH, Park S, Hwang JR, Kim YC, Jun Kim Y, Cho Y, Sun Jin M, Park SG. Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly. Nat Commun. 2019 May 16;10(1):2184.

[10]Shen T, Huang S. Repositioning the Old Fungicide Ciclopirox for New Medical Uses. Curr Pharm Des. 2016;22(28):4443-50.