Zileuton
(Synonyms: 齐留通; A 64077; Abbott 64077) 目录号 : GC16014A reversible inhibitor of 5-lipoxygenase
Cas No.:111406-87-2
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment [1]: | |
Cell lines |
H9c2 cells |
Preparation method |
The solubility of this compound in DMSO is > 13.3 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
Reacting condition |
0 ~ 100 μM; 0 ~ 24 hrs |
Applications |
Zileuton induced COX-2 protein expression in time- and dose-dependent manners without changing the COX-1 protein level. After the treatment with 50 μM Zileuton for 5 hrs, the level of COX-2 protein peaked and sustained for up to 12 hrs. In addition, Zileuton treatment significantly inhibited the induction of cell death by H2O2. |
Animal experiment [2]: | |
Animal models |
A rat permanent MCAO model |
Dosage form |
50 mg/kg; p.o. |
Applications |
In a rat permanent MCAO model, Zileuton significantly reduced the neurological deficit and the cerebral infarction volume. HE staining showed that Zileuton reduced necrotic or ischemic injured neurons. In addition, Zileuton also markedly reduced MCAO-induced increases of MPO activity, MDA content, NF-κB p65 immuno-positive cells, iNOS mRNA and iNOS protein expression, as well as serum TNF-α and IL-1β levels. |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Hyun-Jeong Kwak, Kyoung-Mi Park, Hye-Eun Choi, Hyun-Joung Lim, Jin-Hee Park, Hyun-Young Park. The cardioprotective effects of zileuton, a 5-lipoxygenase inhibitor, are mediated by COX-2 via activation of PKCδ. Cellular Signalling 22 (2010) 80-87. [2]. Tu XK, Yang WZ, Wang CH, Shi SS, Zhang YL, Chen CM, Yang YK, Jin CD, Wen S.Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats. Inflammation. 2010;33(5):344-52. |
IC50: Zileuton inhibited 5-hydroxyeicosatetraenoic aicd synthesis in rat basophilic leukemia cell and polymorphonuclear leukocytes (IC50 = 0.5 and 0.3 μM), respectively [1].
5-Lipoxygenase pathway is to form leukotrienes, including leukotriene B4 (LTB4), 5-oxo-6E,8Z,11Z,14Z-eicosatetranoic acid and the cysteinyl leukotrienes (LTC4, LTD4 and LTE4) and activates all four leukotriene receptors, BLT1, BLT2, cysLT1 and cysLT2. Zileuton is the only commercially available inhibitor of the 5-Lipoxygenase pathway.
In vitro: Treatment of H9c2 cells with zileuton efficiently induced COX-2 expression and PGE2 biosynthesis in a time- and dose-dependent manner. Zileuton also exerted a profound protective effect against H2O2-induced oxidative stress, a mimic of reperfusion damage in vitro, and this protective effect was abolished by COX-2-selective inhibitor. Furthermore, zileuton-stimulated ERK1/2 and Akt phosphorylation was attenuated by rottlerin, indicating that PKCδ might act upstream of ERK1/2 and Akt. These results suggest that zileuton-induced COX-2 expression is sequentially mediated through PKCδ-dependent activation of ERK1/2 and Akt. Based on these findings, we propose that zileuton might provide a new therapeutic strategy for ischemia/reperfusion injury of the heart [2].
In vivo: To investigate the mechanism underlying zileuton's neuroprotection, SD rats underwent permanent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. Zileuton was found to significantly reduce neurological deficit scores, cerebral infarct volume, MPO activity, and the lipid peroxidation levels. It also inhibited the expression of NF-kappaB and decreased the expression and activity of iNOS in rat brain. In addition, zileuton attenuated the release of TNF-alpha and IL-1beta in serum. These results suggested that zileuton reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect of zileuton in cerebral ischemia might be associated with the inhibition of inflammatory reaction [3].
Clinical trial:
Zileuton (trade name ZYFLO) is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation. Zileuton is used for the maintenance treatment of asthma. Zileuton was introduced in 1996 by Abbott Laboratories and is now marketed in two formulations by Cornerstone Therapeutics Inc. under the brand names ZYFLO and ZYFLO CR. Given the important role that leukotrienes play in airway inflammation, zileuton provides an additional therapeutic option in the management of chronic, persistent asthma, particularly those asthmatics with more severe disease. In addition, zileuton has shown promise in a number of other conditions, including upper airway inflammatory conditions, dermatological disease and chronic obstructive pulmonary disease. The development of new formulations, including a controlled release tablet formulation for b.i.d. dosing and an intravenous preparation for acute asthma exacerbations may enhance clinical utility and expand therapeutic indications.
Reference:
[1] Carter GW, Young PR, Albert DH, Bouska J, Dyer R, Bell RL, Summers JB, Brooks DW. 5-lipoxygenase inhibitory activity of zileuton. J Pharmacol Exp Ther. 1991;256(3):929-37.
[2] Hyun-Jeong Kwak, Kyoung-Mi Park, Hye-Eun Choi, Hyun-Joung Lim, Jin-Hee Park, Hyun-Young Park. The cardioprotective effects of zileuton, a 5-lipoxygenase inhibitor, are mediated by COX-2 via activation of PKCδ. Cellular Signalling 22 (2010) 80-87
[3] Tu XK, Yang WZ, Wang CH, Shi SS, Zhang YL, Chen CM, Yang YK, Jin CD, Wen S.Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats. Inflammation. 2010;33(5):344-52.
Cas No. | 111406-87-2 | SDF | |
别名 | 齐留通; A 64077; Abbott 64077 | ||
化学名 | 1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea | ||
Canonical SMILES | CC(C1=CC2=CC=CC=C2S1)N(C(=O)N)O | ||
分子式 | C11H12N2O2S | 分子量 | 236.29 |
溶解度 | ≥ 13.3mg/mL in DMSO, ≥ 12.73 mg/mL in EtOH | 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 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 4.2321 mL | 21.1604 mL | 42.3209 mL |
5 mM | 0.8464 mL | 4.2321 mL | 8.4642 mL |
10 mM | 0.4232 mL | 2.116 mL | 4.2321 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 | |||
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% 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。
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