U-75302
目录号 : GC41289A BLT1 receptor antagonist
Cas No.:119477-85-9
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
U-75302 is an LTB4 receptor antagonist with a Ki of 159 nM on guinea pig lung membranes. This activity is specific for the BLT1 receptor; U-75302 does not antagonize the binding of [3H]-LTB4 to the human BLT2 receptor.
| Cas No. | 119477-85-9 | SDF | |
| Canonical SMILES | OCCCC[C@H](O)CC1=NC(/C=C/[C@H](O)C/C=C\CCCCC)=CC=C1 | ||
| 分子式 | C22H35NO3 | 分子量 | 361.5 |
| 溶解度 | DMF: > 7.1 mg/ml,DMSO: > 10 mg/ml,Ethanol: > 50 mg/ml,PBS 7.2: > 80 µ g/ml | 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 | 2.7663 mL | 13.8313 mL | 27.6625 mL |
| 5 mM | 0.5533 mL | 2.7663 mL | 5.5325 mL |
| 10 mM | 0.2766 mL | 1.3831 mL | 2.7663 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。
Effect of the selective leukotriene B4 antagonist U-75302 on antigen-induced bronchopulmonary eosinophilia in sensitized guinea pigs
Am Rev Respir Dis 1989 Dec;140(6):1712-6.PMID:2557787DOI:10.1164/ajrccm/140.6.1712.
The selective leukotriene B4 (LTB4) antagonist, U-75302, 6-(6-(3-hydroxy-1E,5Z-undecadien-1-yl)-2-pyridinyl)-1,5-hexa nediol) was examined for its ability to inhibit the "late-phase" bronchopulmonary eosinophilia that occurs 6 to 24 h after inhalation of specific antigen in sensitized guinea pigs. Groups of 6 male guinea pigs, sensitized with ovalbumin, were pretreated with U-75302, 1.0, 10.0, or 30.0 mg/kg, or vehicle 1 h before and 7 h after antigen inhalation. Twenty-four hours after antigen provocation, the lungs were lavaged for the enumeration of inflammatory cell populations. Doses of U-75302 (1.0, 10.0 and 30.0 mg/kg) administered orally produced 12.2%, (p greater than 0.05), 43.2% (p less than 0.05), and 61.1% (p less than 0.05) inhibition, respectively, of the antigen-induced influx of eosinophils into the bronchial lumen. Neutrophil populations were not significantly affected by treatment with U-75302. In a separate study, we compared the histopathological changes that occurred following antigen challenge in U-75302-treated or vehicle-treated guinea pigs. Vehicle-treated, sensitized animals exhibited marked changes in the airway at 8 min, 6 h, and 24 h after antigen challenge. U-75302 treatment produced a significant reduction in eosinophil adherence to peribronchial/peribronchiolar capillaries followed by a dramatic and specific reduction of peribronchial eosinophil infiltration (81% reduction at 6 h and 79% reduction at 24 h). Neutrophil migration appeared unaffected. These data implicate LTB4 as a mediator of antigen-induced bronchopulmonary eosinophilia in the guinea pig.
Dual role of leukotriene B4 receptor type 1 in experimental sepsis
J Surg Res 2015 Feb;193(2):902-8.PMID:25439504DOI:10.1016/j.jss.2014.09.013.
Background: The controversial results from different studies suggested that leukocyte recruitment mediated by leukotriene B4 (LTB4) and its receptor might improve pathogen clearance, but might also aggravate organ injury during sepsis. The present study was performed to compare the effect of BLT1 ligand LTB4 and its antagonist U-75302 on the development of sepsis. Methods: Sepsis in mice was induced by cecal ligation and puncture (CLP). The mice were allocated into sham group, CLP group, U-75302 group, and LTB4 group. In the latter three groups, CLP mice were treated by intraperitoneal saline, U-75302, and LTB4, respectively. Their effect on the progression of sepsis were compared by histopathologic tests, level of systemic cytokines, counts of immune cells and bacterial clearance, and survival rate. Results: The histopathologic tests showed that U-75302 attenuated lung injury, whereas LTB4 aggravated liver injury. LTB4 increased the plasma levels of interleukin-6, tumor necrosis factor-α, and U-75302 increased the level of plasma interleukin-10. LTB4 increased whereas U-75302 reduced the neutrophil numbers in the peritoneal lavage fluid. LTB4 also increased the number of peritoneal and splenic CD4(+) and CD8(+) T cells. Bacterial clearance in blood and peritoneal lavage fluid was significantly enhanced in the LTB4 group. Both U-75302 and LTB4 did not change the survival rate significantly compared with vehicle, but mortality in the LTB4 group was significantly higher than in the U-75302 group. Dose response analyses were also performed to compare the effect of U-75302 and LTB4 at different doses. Different doses of both agents did not influence the survival rate of CLP mice. Conclusions: U-75302 attenuates sepsis-induced organ injury, whereas LTB4 increases the leukocyte recruitment toward infection site, but LTB4 showed a more lethal effect than U-75302 during polymicrobial sepsis.
Receptor antagonism of leukotriene B4 myotropic activity by the 2,6 disubstituted pyridine analog U-75302: characterization on lung parenchyma strips
J Lipid Mediat 1989 Jan-Feb;1(1):3-12.PMID:2562431doi
Leukotriene B4 constricts guinea pig lung parenchyma strips in a concentration-dependent manner. The LTB4 structural analog U-75302, 6-(6-[3-hydroxy-1E,5 Z-undecadienyl]-2-pyridinyl)-1,5-hexanediol, was a partial agonist in this system with a potency 300-1000 times less than LTB4. U-75302 constricted lung parenchyma strips only at concentrations greater than 0.3 microM. At concentrations lacking agonist activity U-75302 was an effective antagonist, displacing the LTB4 dose-response curve. Half-maximal responses required 0.10 microM LTB4 in the presence of 0.3 microM U-75302 and 0.01-0.02 microM LTB4 in its absence. The maximal force of contraction was unaffected at this concentration. Concurrent with antagonism of the myotropic response, U-75302 inhibited the LTB4-dependent release of thromboxane B2 from lung parenchyma. This effect was attributable to receptor antagonism, not enzymatic inhibition of phospholipase, cyclooxygenase, or thromboxane synthase. For instance, 0.3 microM U-75302 did not inhibit thromboxane B2 formation by lung parenchyma stimulated with calcium ionophore A23187 and it did not inhibit thromboxane B2 formation by human platelets stimulated with arachidonic acid. U-75302 selectively antagonized the activity of LTB4 and not other myotropic agonists including the thromboxane A2 mimetic U-46619, LTC4, LTD4, AGEPC, PGF2 alpha, and histamine. Receptor antagonists of leukotriene B4 may have multiple beneficial effects on asthmatic or respiratory disorders. These include (i) direct antagonism of LTB4 myotropic actions; (ii) antagonism of LTB4-dependent mediator release; and (iii) antagonism of LTB4 chemotactic action associated with leukocyte infiltration during anaphylactic late phase reactions.
Leukotrienes modulate cytokine release from dendritic cells
Immunology 2005 Dec;116(4):418-28.PMID:16313356DOI:10.1111/j.1365-2567.2005.02241.x.
Leukotriene B(4) (LTB(4)) and cysteinyl leukotrienes (CysLTs) are known as potent mediators of inflammation, whereas their role in the regulation of adaptive immunity remains poorly characterized. Dendritic cells (DCs) are specialized antigen-presenting cells, uniquely capable to initiate primary immune responses. We have found that zymosan, but not lipopolysaccharide (LPS) stimulates murine bone marrow-derived dendritic cells (BM-DCs) to produce large amounts of CysLTs and LTB(4) from endogenous substrates. A selective inhibitor of leukotriene synthesis MK886 as well as an antagonist of the high affinity LTB(4) receptor (BLT(1)) U-75302 slightly inhibited zymosan-, but not LPS-stimulated interleukin (IL)-10 release from BM-DCs. In contrast, U-75302 increased zymosan-stimulated release of IL-12 p40 by approximately 23%. Pre-treatment with transforming growth factor-beta1 enhanced both stimulated leukotriene synthesis and the inhibitory effect of U-75302 and MK886 on IL-10 release from DCs. Consistent with the effects of leukotriene antagonists, exogenous LTB(4) enhanced LPS-stimulated IL-10 release by approximately 39% and inhibited IL-12 p40 release by approximately 22%. Both effects were mediated by the BLT(1) receptor. Ligands of the high affinity CysLTs receptor (CysLT(1)), MK-571 and LTD(4) had little or no effect on cytokine release. Agonists of the nuclear LTB(4) receptor peroxisome proliferator-activated receptor-alpha, 8(S)-hydroxyeicosatetraenoic acid and 5,8,11,14-eicosatetraynoic acid, inhibited release of both IL-12 p40 and IL-10. Our results indicate that both autocrine and paracrine leukotrienes may modulate cytokine release from DCs, in a manner that is consistent with previously reported T helper 2-polarizing effects of leukotrienes.
Contribution of leukotriene B4 to airway inflammation and the effect of antagonists
Ann N Y Acad Sci 1991;629:274-87.PMID:1659282DOI:10.1111/j.1749-6632.1991.tb37983.x.
Inhalation of aerosols of ovalbumin in sensitized guinea pigs produced a marked, bronchoalveolar eosinophilia 24 hr after challenge. The lung eosinophilia was not prevented by the cyclooxygenase inhibitors, indomethacin or PAF antagonists (WEB-2086 and L-652731) but was inhibited by methylprednisolone, the 5-LO inhibitor, U-66858 and a series of structural analogs of LTB4, U-75302, U-77692, U-75485 and U-78489. The effectiveness of LTB4 antagonists but not PAF antagonists in vivo was consistent with in vitro studies in which LTB4 was shown to be far more chemotactic than PAF for guinea pig eosinophils. LTB4 elicited maximal directional migration of guinea pig eosinophils at concentrations from 10(-7) M to 10(-9) M while PAF showed no effect over the same concentration range. The structural analogs of LTB4 were shown to inhibit LTB4 induced chemotaxis of guinea pig eosinophils and produced a dose-related inhibition of binding of LTB4 to guinea pig eosinophil membranes. To add further proof to the hypothesis that LTB4 contributed to the antigen-induced lung eosinophilia we attempted to measure LTB4 release into BAL fluid immediately after and at various time points up to 24 hr after antigen inhalation. However, using a sensitive radioimmunoassay (detection limit 10 pg/ml) very low levels of LTB4 (24.9-67.9 pg/ml) or its metabolite, 20-OH LTB4 (24.9-98.2 pg/ml) were detected in BAL fluid and these levels did not increase significantly following antigen provocation. Inhalation of LTB4 aerosols in unsensitized Brown-Norway rats or inhalation of aerosols of ovalbumin in sensitized Brown-Norway rats also produced a marked "late-phase" eosinophil-rich influx of inflammatory cells into the lungs. The lung eosinophilia in the rat was prevented by two structurally unrelated leukotriene B4 (LTB4) antagonists, U-75302 and Ly255283. These data implicate LTB4 as a mediator of allergen-induced bronchopulmonary eosinophilia. Leukotriene B4 antagonists may provide leads for the development of compounds which inhibit the chronic airway inflammation associated with asthma in man.