Desisobutyryl-ciclesonide
(Synonyms: 去异丁基环索奈德,CIC-AP; Ciclesonide active principle) 目录号 : GC35843
A glucocorticoid receptor agonist and the active metabolite of ciclesonide
Cas No.:161115-59-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment: |
Peripheral blood mononuclear cells are isolated from non atopic and atopic asthmatic children sensitized to Phleum pratense (PhlP5). Proliferation toward Candida albicans or PhlP5 in the presence of Ciclesonide or Desisobutyryl-ciclesonide (0.003-3.0 μM) is evaluated as [3H]thymidine incorporation. Modulation of PhlP5-specific T-cell blasts proliferation and PhlP5-induced interleukin 4 expression by Ciclesonide and Desisobutyryl-ciclesonide are measured[1]. |
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References: [1]. Silvestri M, et al. Ciclesonide modulates in vitro allergen-driven activation of blood mononuclear cells and allergen-specific T-cell blasts. Immunol Lett. 2012 Jan 30;141(2):190-6. |
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Desisobutyryl ciclesonide is a glucocorticoid receptor agonist and the active metabolite of the prodrug ciclesonide .1,2 It is formed from inhaled ciclesonide by intracellular esterases in the lung. Desisobutyryl ciclesonide binds to the glucocorticoid receptor (IC50 = 1.75 nM for the human receptor) and induces glucocorticoid receptor-mediated gene transactivation in a reporter assay. It inhibits concanavalin A-induced proliferation of primary rat spleen cells and human peripheral blood mononuclear cells (PBMCs; IC50s = 1.5 and 1.3 nM, respectively). Desisobutyryl ciclesonide also inhibits CD3-induced proliferation of human CD4+ lymphocytes (IC50 = 0.2 nM) and the production of cytokines in the same cells (IC50s = 0.5-1.5 nM).3 It reduces eosinophil, TNF-α, and total protein accumulation in bronchoalveolar lavage fluid (BALF) of rats sensitized and challenged with ovalbumin (ED50s = 0.7, 0.4, and 0.5 mg/kg, respectively).
1.Belvisi, M.G., Bundschuh, D.S., Stoeck, M., et al.Preclinical profile of ciclesonide, a novel corticosteroid for the treatment of asthmaJ. Pharmacol. Exp. Ther.314(2)568-574(2005) 2.Joshi, T., Johnson, M., Newton, R., et al.An analysis of glucocorticoid receptor-mediated gene expression in BEAS-2B human airway epithelial cells identifies distinct, ligand-directed, transcription profiles with implications for asthma therapeuticsBr. J. Pharmacol.172(5)1360-1378(2015) 3.Stoeck, M., Riedel, R.T., Hochhaus, G., et al.In vitro and in vivo anti-inflammatory activity of the new glucocorticoid ciclesonideJ. Pharmacol. Exp. Ther.309(1)249-258(2004)
| Cas No. | 161115-59-9 | SDF | |
| 别名 | 去异丁基环索奈德,CIC-AP; Ciclesonide active principle | ||
| Canonical SMILES | C[C@@]12[C@@]3(C(CO)=O)[C@](O[C@H](O3)C4CCCCC4)([H])C[C@@]1([H])[C@]5([H])CCC6=CC(C=C[C@]6(C)[C@@]5([H])[C@@H](O)C2)=O | ||
| 分子式 | C28H38O6 | 分子量 | 470.6 |
| 溶解度 | DMSO: ≥ 50 mg/mL (106.25 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1249 mL | 10.6247 mL | 21.2495 mL |
| 5 mM | 0.425 mL | 2.1249 mL | 4.2499 mL |
| 10 mM | 0.2125 mL | 1.0625 mL | 2.1249 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Ciclesonide
Drugs 2004;64(5):511-9; discussion 520-1.PMID:14977388DOI:10.2165/00003495-200464050-00005.
Ciclesonide is an inhaled corticosteroid (delivered via a hydrofluoroalkane metered-dose inhaler) that is converted to an active metabolite, Desisobutyryl-ciclesonide, in the lung, thereby minimising effects on endogenous cortisol. In two 12-week, randomised studies in patients with asthma, ciclesonide 80 or 320 microg once daily was at least as effective as budesonide 400 microg/day at increasing forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline; ciclesonide 320 microg daily was significantly more effective than budesonide 400 microg once daily in one study. In a randomised, double-blind study in patients with asthma controlled with high-dosages of inhaled corticosteroids, FEV(1) and FVC decreased significantly from baseline at 12 weeks in patients receiving ciclesonide 320 microg daily or budesonide 400 microg daily; peak expiratory flow values decreased significantly only in patients receiving budesonide. Inhaled ciclesonide 80 or 320 microg daily improved asthma symptom scores and decreased the use of rescue medication by a similar, significant amount to budesonide 400 microg/day in two 12-week studies. Inhaled ciclesonide was generally well tolerated in patients with asthma. Ciclesonide did not suppress biochemical markers of adrenal function in 52-week studies. The long-term (>52 weeks) systemic effects of ciclesonide remain unknown.
LC-HRMS/MS study of the prodrug ciclesonide and its active metabolite Desisobutyryl-ciclesonide in plasma after an inhalative administration to horses for doping control purposes
Drug Test Anal 2022 Feb;14(2):252-261.PMID:34634175DOI:10.1002/dta.3174.
Ciclesonide (CIC) is the first inhaled highly potent corticosteroid that does not cause any cortisol suppression. It has been developed for the treatment of asthma in human and more recently in equine. CIC is the active compound of Aservo® EquiHaler® (Boehringer Ingelheim Vetmedica GmbH), the pre-filled inhaler generating a medicated mist based on Soft Mist™ technology. This prodrug is rapidly converted to Desisobutyryl-ciclesonide (des-CIC), the main pharmacologically active compound. Due to its anti-inflammatory properties, CIC is prohibited for use in horse competitions. To set up an appropriate control, the determination of detection times and screening limits are required. Therefore, a highly sensitive analytical method based on supported liquid extraction (SLE) combined with liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) was developed to detect CIC and its active metabolite des-CIC in plasma. The lower limit of detection of CIC and des-CIC was approximately 1 pg/ml in plasma. After a pilot study conducted on a single horse at the recommended dose (eight actuations twice daily corresponding to 5.5 mg/day for the first 5 days, followed by 12 actuations once daily corresponding to 4.1 mg/day in the last 5 days), the same protocol was applied in the main study using six horses. In all horses, CIC and des-CIC levels were less than 5 and 10 pg/ml, respectively, at 36 h after the end of the administration. The outcome of this risk assessment study should be useful to draw any recommendations for horse competitions.
Ciclesonide modulates in vitro allergen-driven activation of blood mononuclear cells and allergen-specific T-cell blasts
Immunol Lett 2012 Jan 30;141(2):190-6.PMID:22015638DOI:10.1016/j.imlet.2011.10.003.
Background: Ciclesonide, an inhaled corticosteroid with almost no affinity for the glucocorticoid receptor, is highly effective in downregulating in vitro pro-inflammatory activities of airway parenchymal cells when converted into the active metabolite Desisobutyryl-ciclesonide. Objective: We evaluate whether ciclesonide could effectively downregulate also antigen- or allergen-induced activation of peripheral blood mononuclear cell and of allergen-specific T-cell blasts. Methods: Peripheral blood mononuclear cells were isolated from non atopic and atopic asthmatic children sensitized to Phleum pratense (PhlP5). Proliferation toward Candida albicans or PhlP5 in the presence of ciclesonide or Desisobutyryl-ciclesonide (0.003-3.0 μM) was evaluated as [(3)H]thymidine incorporation. Modulation of PhlP5-specific T-cell blasts proliferation and PhlP5-induced interleukin 4 expression by ciclesonide and Desisobutyryl-ciclesonide were measured. Results: Peripheral blood mononuclear cell proliferation to C. albicans was dose-dependently inhibited by 0.3-3.0 μM ciclesonide and Desisobutyryl-ciclesonide but inhibition by Desisobutyryl-ciclesonide was higher. A significant proliferation to PhlP5 was observed only in cultures from atopic subjects: an effective downregulation was already detected at 0.03 μM ciclesonide and 0.003 μM Desisobutyryl-ciclesonide (complete inhibition at 3 μM ciclesonide and 0.03 μM Desisobutyryl-ciclesonide). 3 μM ciclesonide and Desisobutyryl-ciclesonide reduced the PhlP5-specific T-cell blast proliferation and interleukin 4-producing cell proportion. Conclusions and clinical relevance: These in vitro data, obtained at concentrations similar to those reached in vivo at bronchial level, are in favor of an efficient inhibition of ciclesonide on the T-cell mediated response toward allergens. Additional studies are required to confirm these preliminary data on the reduced activity of the drug on allergen-specific T-cell blast activation that may have clinical relevance.
Ciclesonide: A Pro-Soft Drug Approach for Mitigation of Side Effects of Inhaled Corticosteroids
J Pharm Sci 2016 Sep;105(9):2509-2514.PMID:27339407DOI:10.1016/j.xphs.2016.05.004.
Inhaled corticosteroids are used as one of the first-line drug therapy in patients with asthma. However, their long-term use is associated with various oropharyngeal and systemic side and adverse effects. Design of pro-soft drug is one of the strategies, which was adopted in the design of ciclesonide for mitigation of side effects usually observed with the use of inhaled corticosteroids. Ciclesonide, a pro-soft drug, is converted to an active metabolite Desisobutyryl-ciclesonide in the lungs. The anti-inflammatory effect of Desisobutyryl-ciclesonide is much higher than ciclesonide, and therefore, the local effect of the metabolite is higher with lower systemic side effects. Ciclesonide has favorable pharmacokinetic and pharmacodynamic properties as inhaled corticosteroid including low oral bioavailability, high plasma protein binding and rapid systemic clearance, high pulmonary deposition and distribution and long pulmonary residence duration. These advantageous properties make ciclesonide a very effective treatment option with low side effects. Various clinical studies support safety and efficacy of ciclesonide use in mild, moderate, and severe asthma patients.
Uptake and metabolism of ciclesonide and retention of Desisobutyryl-ciclesonide for up to 24 hours in rabbit nasal mucosa
BMC Pharmacol 2007 Jun 6;7:7.PMID:17553148DOI:10.1186/1471-2210-7-7.
Background: The nasal tissue uptake and metabolism of ciclesonide, a new-generation corticosteroid under investigation for treatment of allergic rhinitis, to its active metabolite, Desisobutyryl-ciclesonide (des-CIC), was evaluated when administered to rabbits in a hypotonic versus an isotonic ciclesonide suspension. Nasal mucosa extracts from normal Japanese white rabbits were evaluated by high-performance liquid chromatography with tandem mass spectrometry detection after a single 143-mug dose of ciclesonide. Retention and formation of fatty acid conjugates of des-CIC were also measured in nasal mucosa extracts postadministration of a hypotonic ciclesonide suspension (143-mug single dose). Results: Versus an isotonic suspension, the hypotonic suspension achieved higher concentrations of des-CIC (5.6-fold, 11.4-fold, and 13.4-fold; p < 0.05 for all) and ciclesonide (25.3-fold, 34.2-fold [p = not significant], and 16-fold [p < 0.05]) at 30, 120, and 240 min postadministration. Additionally, when administered via a hypotonic suspension, des-CIC was retained up to 24 h postadministration (45.46 pmol/g tissue). Highest concentration of major fatty acid ester conjugate, des-CIC-oleate, was detected in nasal mucosa at 8 h postadministration. Conclusion: These data suggest that a hypotonic ciclesonide suspension provides higher intracellular concentrations of des-CIC up to 24 h, thereby providing a rationale for investigation of ciclesonide as a convenient once-daily nasal spray for treatment of allergic rhinitis.