ONO4057 (ONO-LB457)
(Synonyms: ONO-LB457) 目录号 : GC32011
ONO4057 (ONO-LB457) 是一种白三烯 B4 受体拮抗剂，IC50 为 0.&7#177;0.3 μM。
Cas No.:134578-96-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Inbred male ACI (180 to 210 g) and LEW (200 to 240 g) rats are used as donors and recipients. Liver transplantation is orthotopically performed. ONO4057 dissolved in 7% NaHCO3 or solvent is administered subcutaneously daily after transplantation. Animals are divided into two groups: group I (n=5), 7% NaHCO3 3 mL/kg as controls; group II (n=6), ONO4057 30 mg/kg per day[2]. |
References: [1]. Kishikawa K, et al. ONO-4057, a novel, orally active leukotriene B4 antagonist: effects on LTB4-induced neutrophil functions. Prostaglandins. 1992 Oct;44(4):261-75. | |
ONO4057 is a Leukotriene B4 receptor antagonist, with an IC50 of 0.7±0.3 μM.
Mean animal survivals of the ONO4057-treated animals significantly prolong to 21.0±4.4 days compare with 12.0±0.6 days in control group. Histological findings from grafts taken on day 7 show that severe focal cellular infiltration is observed in both groups, but the degree of hepatocyte necrosis in ONO4057-treated anmimals is milder than that in control group[2].
[1]. Kishikawa K, et al. ONO-4057, a novel, orally active leukotriene B4 antagonist: effects on LTB4-induced neutrophil functions. Prostaglandins. 1992 Oct;44(4):261-75. [2]. Tanaka M, et al. Effect of leukotriene B(4) receptor antagonist (ONO4057) on hepatic allografting in rats. Transplant Proc. 2000 Nov;32(7):2340.
| Cas No. | 134578-96-4 | SDF | |
| 别名 | ONO-LB457 | ||
| Canonical SMILES | O=C(O)CCC1=C(OCCCC/C=C/C2=CC=C(OC)C=C2)C=CC=C1OCCCCC(O)=O | ||
| 分子式 | C27H34O7 | 分子量 | 470.55 |
| 溶解度 | Soluble in DMSO | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1252 mL | 10.6259 mL | 21.2517 mL |
| 5 mM | 0.425 mL | 2.1252 mL | 4.2503 mL |
| 10 mM | 0.2125 mL | 1.0626 mL | 2.1252 mL |
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| 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 | ||||||||||
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工作液浓度： mg/ml；
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2.
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[Role of leukotriene B4 in monocrotaline-induced pulmonary hypertension]
Monocrotaline (MCT) causes lung inflammation and chronic pulmonary hypertension associated with lung vascular thickening in rats. We hypothesized that leukotriene B4 (LTB4) and LTB4-induced accumulation of leukocytes in the lung play a role in MCT-induced lung disease, and therefore measured LTB4 and myeloperoxidase (MPO) levels in lung tissue of MCT-treated rats. Next, we examined the effect of an orally active LTB4 receptor antagonist (ONO4057) on MPO levels in lung tissue, on pulmonary hypertension, and on pulmonary vascular remodeling induced by MCT. Lung LTB4 and MPO levels had increased by 3 days after MCT injection. In the ONO4057-treated MCT rats, lung MPO levels were significantly lower than in the rats given MCT but not ONO4057. By the third week after injection. MCT had caused increases in mean pulmonary arterial pressure, in the ratio of right ventricular weight to left ventricle+septum weight (RV/[VS + S]), and in media wall thickness of the muscular arteries of the lung. Treatment with ONO4057, either for 3 weeks or during the first week after MCT injection, significantly reduced pulmonary hypertension, right ventricular hypertrophy, and lung vascular thickening induced by MCT. These results indicate that ONO4057 reduces both the accumulation of leukocytes in lung tissue and the chronic pulmonary hypertension induced by MCT, and they suggest a role for LTB4 in the inflammatory process that contributes to pulmonary hypertension and lung vascular remodeling induced by MCT in rats.
The immunosuppressive effects of a leukotriene B4 receptor antagonist on liver allotransplantation in rats
The immunosuppressive effects of a leukotriene B4 (LTB4) receptor antagonist, ONO4057, on liver allotransplantation in rats were evaluated, and the levels of prostaglandin E2 (PGE2) in the liver tissue during rejection of the allografts examined. The rats were divided into four groups: group 1: Lewis rats (LEW) given a sham operation with dimethyl sulfoxide (DMSO); group 2: LEW given syngenic orthotopic liver transplantation (OLT) from LEW, with DMSO; group 3: LEW given allogenic OLT from ACI rats (ACI), with DMSO; and group 4: LEW given allogenic OLT from ACI, with ONO4057 as 10, 30, or 100 mg/kg per day dissolved in DMSO to subgroups 4a, 4b, and 4c, respectively. Histological examinations were performed, survival times monitored, and liver tissue PGE2 levels 3, 5, 7, and 14 days after transplantation measured. The mean graft survival times in groups 4a, b, and c, at 37.5 +/- 10.4, 52.2 +/- 24.4, and 34.0 +/- 4.9 days (mean +/- SEM), respectively, were significantly longer than that in group 3 (at 13.0 +/- 3.2 days). Moreover, the levels of tissue PGE2 in the liver allografts in group 4a were significantly higher than those in group 3 on days 5 and 7. These results suggest that ONO4057 has an immunosuppressive effect on liver allotransplantation since it reduces the activities of LTB4 which augments immune responses, and also because it indirectly increases the PGE2 level.
Effect of ONO-4057 and tacrolimus on ischemia-reperfusion injury of the liver
Aim: To investigate the effects of a novel Leukotriene B(4) receptor antagonist and/or tacrolimus on ischemia-reperfusion in a rat liver model.
Methods: Male Lewis rats were pretreated with ONO-4057 (100 mg/kg) and/or tacrolimus (1 mg/kg) orally, and divided into four experimental groups; group 1 (control), group 2 (ONO-4057), group 3 (tacrolimus), group 4 (ONO-4057 + tacrolimus).
Results: There was a tendency for long survival in the groups treated with tacrolimus alone and ONO-4057 plus tacrolimus. Post-reperfusion serum aspartate aminotransferase levels decreased more significantly in ONO-4057 plus tacrolimus group (P < 0.01), than in the tacrolimus alone group (P < 0.05), compared to controls.
Conclusion: This study demonstrated that pretreatment with ONO-4057 in combination with tacrolimus produced additive effects in a rat model of liver ischemia-reperfusion injury.
[A Research on Drug Discovery for Intracerebral Hemorrhage Focusing on Leukotriene B4 and Its Receptor]
Intracerebral hemorrhage (ICH) results from blood vessels rupture in the brain, forming a blood clot in the brain parenchyma. Leakage of blood constituents causes detrimental tissue damages, ensuing long-lasting neurological deficits; however, effective therapeutic approaches are not yet developed to date. In this study, leukotriene B4 (LTB4) and its receptor leukotriene B4 receptor 1 (BLT1) are proposed as novel therapeutic targets for ICH therapy. After the onset of ICH, the LTB4 content in the brain transiently elevated. Microglia are considered as the source of LTB4 production. Thrombin, a blood constituent, activated the BV-2 microglia and increased the LTB4 secretion from the BV-2 cells. Microglia-released LTB4 promoted its own microglial activation and neutrophil-like differentiated HL-60 cell migration activity. LTB4 receptors comprised of two types: BLT1 and BLT2, with BLT1 known to be a high-affinity receptor associated with chemotaxis. BLT1 knockout mice showed decreased neutrophil invasion, attenuating sensorimotor dysfunction after ICH. Furthermore, therapeutic administration of ONO-4057, an orally active LTB4 receptor antagonist, attenuated neutrophil invasion, microglial activation, axonal fragmentation, and sensorimotor deficits induced by ICH. These results suggest that LTB4 and its receptor BLT1 can be potential promising therapeutic targets that prevent tissue damages following ICH.
Role of leukotrienes in post-allergic propranolol-induced bronchoconstriction in guinea-pigs
Background: Administration of propranolol can provoke bronchoconstriction only in asthmatic patients. Recently we developed an animal model for propranolol-induced bronchoconstriction (PIB). Our working hypothesis is that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction.
Objectives: Our goal in this study was to determine which products of arachidonate 5-lipoxygenase pathway are involved in the PIB.
Methods: Propranolol at a concentration of 10 mg/mL was inhaled 20 min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea-pigs. Two different sulfidopeptide leukotriene (s-LT) antagonists, ICI198 615 in the doses of 0.03 and 0.3 mg/kg and vehicle and KCA757 in the doses of 1 and 5 mg/kg and vehicle, and a LTB4 antagonist ONO4057 in the doses of 1 and 10 mg/kg and vehicle were injected intravenously 15 min after antigen challenge. Effects of an anticholinergic agent atropine sulphate (5mg/kg) and an alpha-adrenergic blocker phentolamine (0.3 and 3 mg/kg) were examined in the same way.
Results: Bronchoconstriction occurred when 10 mg/mL of propranolol was inhaled 20 min after antigen challenge. Both ICI198 615 and KCA757 administered intravenously 15 min after antigen challenge reduced the PIB in a dose-dependent manner while ONO4057 did not alter the PIB. Atropine or phentolamine did not change the PIB.
Conclusions: These results suggest that mediator mechanism, but not cholinergic or alpha-adrenergic nerve, is important in the PIB which developed after the allergic bronchoconstriction in our guinea-pig model and that s-LTs but not LTB4 have an important role in the pathophysiology of the PIB.