Pranlukast hemihydrate is a highly potent, selective and competitive antagonist of peptide leukotrienes. Pranlukast inhibits [³H]LTE₄, [³H]LTD₄, and [³H]LTC₄ bindings to lung membranes with K_is of 0.63±0.11, 0.99±0.19, and 5640±680 nM, respectively.

In the radioligand binding assay, Pranlukast (ONO-1078) inhibits [³H]LTE₄, [³H]LTD₄, and [³H]LTC₄ bindings to lung membranes with K_is of 0.63±0.11, 0.99±0.19, and 5640±680 nM, respectively. The antagonism of Pranlukast against [³H]LTD₄ binding is competitive. In functional experiments, Pranlukast shows competitive antagonism against the LTC₄– and LTD₄-induced contractions of guinea pig trachea and lung parenchymal strips with a pA₂ range of 7.70 to 10.71. In the presence of an inhibitor of the bioconversion of LTC₄ to LTD₄, Pranlukast also antagonizes the LTC₄-induced contraction of guinea pig trachea (pA₂=7.78). Pranlukast significantly reverses the LTD₄-induced prolonged contraction without effect on the KCl- and BaCl₂-induced contractions of guinea pig trachea^[1]. Oxygen-glucose deprivation (OGD)-induced nuclear translocation of CysLT₁ receptors is inhibited by pretreatment with the CysLT₁ receptor antagonist Pranlukast (10 μM). Pranlukast protects endothelial cells against ischemia-like injury. The effects of the CysLT₁ receptor antagonist Pranlukast and the 5-lipoxygenase inhibitor Zileuton on translocation are also assessed. The results show that Pranlukast, but not Zileuton, inhibits the translocation of the CysLT₁ receptor 6 h after OGD^[2].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Carrageenan (CAR, 5 mg per mouse) is injected i.p. 24 h before LPS (50 p,g per mouse) is injected i.v. Various doses of Pranlukast (ONO-1078; 40, 20, and 10 mmol/kg), AA-861 (20, 10, and 5 mmol/kg), Indomethacin (40 mmollkg), and the controls are injected s.c. into mice 30 min before they are challenged with 50 p,g of LPS. The maximum soluble doses are 0.6 mmol/mL in 10% DMSO for AA-861 and 1.2 mmol/mL in 10% ethanol for Pranlukast. These solutions are used as the maximum doses for the treatments. The mortality of mice is significantly decreased in AA-861- Pranlukast-treated mice relative to that in the control mice. Pretreatment with CAR (5 mg i.p.) renders the mice more sensitive to the effect of LPS. Although the survival rate of mice treated with each solvent is 20% at 72 h after LPS (50 p,g per mouse) administration, s.c. treatment with AA-861 (20 mmol/kg) or Pranlukast (40 mmol/kg) significantly increases the survival rate after the LPS administration (AA-861, P<0.001; Pranlukast, P<0.01)^[3].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

490.51

C₂₇H₂₃N₅O₄.1/2H₂O

150821-03-7

固体

White to off-white

普鲁司特半水合物

• Alkaloids
• Other Alkaloids

• 内源性代谢物

Room temperature in continental US; may vary elsewhere.

DMSO 中的溶解度 : 25 mg/mL (50.97 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

H₂O 中的溶解度 : < 0.1 mg/mL (insoluble)

* 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, 2 years; -20°C, 1 year。-80°C储存时，请在2年内使用， -20°C储存时，请在1年内使用。

• 方案 一

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in Saline)

  Solubility: 2.5 mg/mL (5.10 mM); 悬浊液; 超声助溶

  此方案可获得 2.5 mg/mL的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中，混合均匀。

  20% SBE-β-CD in Saline 的配制（4°C，储存一周）：2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。

• [1]. Obata T, et al. In vitro antagonism of ONO-1078, a newly developed anti-asthma agent, against peptide leukotrienes in isolated guinea pig tissues. Jpn J Pharmacol. 1992 Nov;60(3):227-37.  [Content Brief]

  [2]. Fang SH, et al. Nuclear translocation of cysteinyl leukotriene receptor 1 is involved in oxygen-glucose deprivation-induced damage to endothelial cells. Acta Pharmacol Sin. 2012 Dec;33(12):1511-7.  [Content Brief]

  [3]. Ogata M, et al. Protective effects of a leukotriene inhibitor and a leukotriene antagonist on endotoxin-induced mortality in carrageenan-pretreated mice. Infect Immun. 1992 Jun;60(6):2432-7.  [Content Brief]

EA.hy926 cells are cultured in Dulbecco’s modified Eagle’s medium (DMEM), supplemented with 10% heat-inactivated fetal calf serum, Penicillin (100 U/mL) and Streptomycin (100 mg/mL). Experiments are conducted 24 h after cells are seeded. OGD is performed. Briefly, the original medium is removed; the cells are washed twice with glucose-free Earle’s balanced salt solution (EBSS) and placed in fresh glucose-free EBSS. Cultures are then placed in an incubator containing 5% CO₂ and 95% N₂ at 37°C for 2 to 8 h. Control cultures are maintained in glucose-containing EBSS under normal conditions. 10 μM Pranlukast, 10 μM Zileuton, a 5-LOX inhibitor or 10 μM Pyrrolidine dithiocarbamate (PDTC), is added to the culture 30 min before OGD exposure and maintained during OGD^[2].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[3]
Male ddY mice are used. All mice used are 7 to 8 weeks of age. Endotoxin shock is induced in mice. In brief, CAR (5 mg in 0.5 mL of physiological saline) is injected intraperitoneally (i.p.) as a priming agent 24 h before LPS challenge. LPS (50 p,g in 0.5 mL of physiological saline) is injected intravenously into the tail vein as an inducing agent. The indicated doses of AA-861, Pranlukast (40, 20, and 10 mmol/kg), saline, DMSO, or ethanol are administrated subcutaneously (s.c.) in a volume of 1 mL into the backs of mice 30 min before the LPS provocation. Both drugs are injected s.c., because CAR i.p. pretreatment caused peritonitis. To examine the role of endogenous TNF in CAR pretreated mice, 2×10⁵ U of rabbit anti-TNF-a antibody or normal serum of rabbit in 0.2 mL is injected intravenously (i.v.) before the LPS challenge^[3].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Obata T, et al. In vitro antagonism of ONO-1078, a newly developed anti-asthma agent, against peptide leukotrienes in isolated guinea pig tissues. Jpn J Pharmacol. 1992 Nov;60(3):227-37.  [Content Brief]

  [2]. Fang SH, et al. Nuclear translocation of cysteinyl leukotriene receptor 1 is involved in oxygen-glucose deprivation-induced damage to endothelial cells. Acta Pharmacol Sin. 2012 Dec;33(12):1511-7.  [Content Brief]

  [3]. Ogata M, et al. Protective effects of a leukotriene inhibitor and a leukotriene antagonist on endotoxin-induced mortality in carrageenan-pretreated mice. Infect Immun. 1992 Jun;60(6):2432-7.  [Content Brief]