| Size | Price | |
|---|---|---|
| 50mg | ||
| Other Sizes |
| Targets |
LTE4 ( Ki = 0.63 nM ); LTD4 ( Ki = 0.99 nM ); LTC4 ( Ki = 5640 nM )
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|---|---|
| ln Vitro |
In radioligand binding tests, Pranlukast (ONO-1078) suppresses the binding of [3H]LTE4, [3H]LTD4, and [3H]LTC4 to lung membranes with Kis of 0.63±0.11, 0.99±0.19, and 5640±680 nM, respectively. ..The antagonism of [3H]LTD4 binding by Pranlukast is competitive. In functional studies, Pranlukast competitively antagonized LTC4- and LTD4-induced contraction of guinea pig trachea and lung parenchymal strips, with pA2 ranging from 7.70 to 10.71. Pranlukast also antagonized LTC4-induced tracheal constriction in guinea pigs (pA2=7.78) in the presence of inhibitors of LTC4 bioconversion to LTD4. Pranlukast substantially reverses LTD4-induced extended contraction without affecting KCl and BaCl2-induced guinea pig tracheal contraction [1]. Pretreatment with the CysLT1 receptor antagonist Pranlukast (10 μM) reduces oxygen glucose deprivation (OGD)-induced CysLT1 receptor nuclear translocation. Pranlukast protects endothelial cells against ischemia-like damage. The effects of the CysLT1 receptor antagonist Pranlukast and the 5-lipoxygenase inhibitor Zileuton on translocation were also examined. The results demonstrated that pranlukast, but not zileuton, reduced CysLT1 receptor translocation 6 hours after OGD [2].
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| ln Vivo |
Mice were subcutaneously injected with different doses of pranlukast (ONO-1078; 40, 20 and 10 mmol/kg), AA-861 (20, 10 and 5 mmol/kg), indomethacin (40 mmol/kg), and control 30 minutes prior to the intravenous injection of 50 μg LPS. Carrageenan (CAR, 5 mg per mouse) was injected intraperitoneally 24 hours before the LPS injection (50 p,g per mouse). ..In 10% DMSO, the maximum soluble concentration of AA-861 is 0.6 mmol/mL, while in 10% ethanol, the maximum soluble concentration of Pranlukast is 1.2 mmol/mL. These solutions serve as the treatment's maximal dosages. Compared to control mice, mice treated with AA-861-pranlukast exhibited a significant decrease in mortality. Mice treated with CAR (5 mg ip) prior to LPS exposure showed increased sensitivity to its effects. The survival rate of mice treated with either AA-861 (20 mmol/kg) or pranlukast (40 mmol/kg) subcutaneous treatment significantly increased survival rate after LPS administration (AA-861, P<0.001; Pranlukast, P<0.01), despite the fact that the survival rate of mice treated with each solvent was only 20% at 72 hours after LPS (50 p,g per mouse) administration [3].
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| Enzyme Assay |
In this study, researchers evaluated the antagonist activity of Pranlukast/ONO-1078 against peptide leukotrienes (LTs) by a radioligand binding assay and functional experiments in guinea pigs. In the radioligand binding assay, ONO-1078 inhibited [3H]LTD4 and [3H]LTE4 bindings to lung membranes (Ki = 0.99 and 0.63 nM, respectively) and was 2,000- to 3,000-fold more potent than FPL55712. Antagonism of ONO-1078 against [3H]LTC4 binding (Ki = 5640 nM) was approximately twofold more potent than that of FPL55712. The antagonism of ONO-1078 against [3H]LTD4 binding was competitive. In functional experiments, ONO-1078 showed 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 and was approximately 400- to 3,300-fold more potent than FPL55712. Interestingly, in the presence of an inhibitor of the bioconversion of LTC4 to LTD4, ONO-1078 also antagonized the LTC4-induced contraction of guinea pig trachea (pA2 = 7.78). ONO-1078 significantly reversed the LTD4-induced prolonged contraction without effect on the KCl- and BaCl2-induced contractions of guinea pig trachea. Furthermore, ONO-1078 antagonized the antigen-induced SRS-A mediated contraction of guinea pig trachea. On the other hand, ONO-1078 showed no antagonism against histamine, acetylcholine, 5-hydroxytryptamine, prostaglandin D2 and U-46619. In addition, ONO-1078 showed little or no effect on the activities of cyclooxygenase, 5-lipoxygenase and thromboxane synthetase. These in vitro studies indicate that ONO-1078 is a highly potent, selective and competitive antagonist of peptide leukotrienes that acts with higher affinity at LTD4 and LTE4 receptors than LTC4 receptors[1].
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| Cell Assay |
EA.hy926 cells were cultured in Dulbecco's modified Eagle's medium, supplemented with 10% heat-inactivated fetal calf serum, penicillin (100 U/mL) and streptomycin (100 mg/mL). Experiments were conducted 24 h after cells were seeded.
oxygen-glucose deprivation (OGD) was performed as described previously. Briefly, the original medium was removed; the cells were washed twice with glucose-free Earle's balanced salt solution (EBSS) and placed in fresh glucose-free EBSS. Cultures were then placed in an incubator containing 5% CO2 and 95% N2 at 37 °C for 2 to 8 h. Control cultures were maintained in glucose-containing EBSS under normal conditions. Ten μmol/L Pranlukast/ONO-1078, 10 μmol/L zileuton, a 5-LOX inhibitor or 10 μmol/L pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, was added to the culture 30 min before OGD exposure and maintained during OGD.[2]
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| Animal Protocol |
The leukotrienes and tumor necrosis factor (TNF) play an important role in the pathophysiology of septic shock, in which hypotension, leukopenia, thrombocytopenia, and hemoconcentration are observed. This study was performed to examine the effects of a 5-lipoxygenase inhibitor (AA-861), a selective leukotriene receptor antagonist (Pranlukast/ONO-1078), and a cyclooxygenase inhibitor (indomethacin) on endotoxin-induced mortality and TNF production in mice. Mice were injected intraperitoneally with carrageenan (5 mg per mouse), which we previously reported as an effective priming agent for lipopolysaccharide (LPS)-induced TNF production and mortality (M. Ogata, S. Yoshida, M. Kamochi, A. Shigematsu, and Y. Mizuguchi, Infect. Immun. 59:679-683, 1991). The indicated doses of AA-861, Pranlukast/ONO-1078, indomethacin, or controls were administrated subcutaneously 30 min before LPS (50 micrograms per mouse) provocation. The mortality of mice was significantly decreased by pretreatment with AA-861 (P less than 0.001) or Pranlukast/ONO-1078 (P less than 0.01) but not by pretreatment with indomethacin. The 50% lethal dose of LPS in the mice treated with dimethyl sulfoxide or ethanol was 32 or 33 micrograms, respectively, and it increased to 83 micrograms with AA-861 or 59 micrograms with Pranlukast/ONO-1078, respectively. Neither AA-861 nor Pranlukast/ONO-1078 suppressed LPS-induced TNF production in sera. Treatment with AA-861 significantly decreased the leukopenia and thrombocytopenia, and Pranlukast/ONO-1078 significantly decreased the hemoconcentration and thrombocytopenia. The role of endogenous TNF was also examined in the carrageenan-pretreated mice. Treatment with 2 x 10(5) U of rabbit anti TNF-alpha antibody intravenously 2 h before LPS challenge significantly suppressed the LPS-induced TNF activity and decreased the mortality. Therefore, both leukotrienes and TNF play important roles in endotoxin-induced shock and mortality.[3]
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| References |
|
| Additional Infomation |
Objective: Cysteinyl leukotriene receptor 1 (CysLT(1) receptor) is localized in epithelial cells and translocates from the plasma membrane to the nucleus in a ligand-dependent manner. This study aimed to investigate whether CysLT(1) receptor translocates to the nucleus in endothelial cells after in vitro ischemic injury and whether it participates in endothelial cell ischemia-reperfusion injury. Methods: EA.hy926 cell line derived from human umbilical vein endothelial cells was treated with oxygen-glucose deprivation (OGD). The expression and distribution of CysLT(1) receptor were detected by immunofluorescence staining, immunogold labeling, and Western blotting. Cell viability was assessed by MTT assay. Cell necrosis and apoptosis were detected by propidium iodide and Hoechst 33342 dual fluorescence staining. Results: In EA.hy926 cells, CysLT(1) receptor was mainly distributed in the cytoplasm and nucleus, with only a small amount distributed on the cell membrane. OGD treatment induced the translocation of CysLT(1) receptor from the cytoplasm to the nucleus in a time-dependent manner, reaching a peak at 6 hours. Pretreatment with the CysLT(1) receptor antagonist pranlast (10 μmol/L) or pre-incubation with NLS-pep (a peptide corresponding to the nuclear localization sequence of the CysLT(1) receptor, 10 μg/mL) inhibited OGD-induced CysLT(1) receptor nuclear translocation. However, zilouton (a 5-lipoxygenase inhibitor, which is a key enzyme in the production of cysteyl leukotrienes) did not inhibit CysLT(1) receptor nuclear translocation. In addition, pre-incubation with NLS-pep (0.4 μg/mL) significantly improved OGD-induced cell viability decline and necrosis. Conclusion: After in vitro ischemic injury, the CysLT(1) receptor in endothelial cells translocates to the nucleus in a ligand-independent manner and participates in ischemic injury. [2]
|
| Molecular Formula |
C27H23N5O4.H2O
|
|---|---|
| Molecular Weight |
499.5179
|
| Exact Mass |
980.36
|
| CAS # |
150821-03-7
|
| Related CAS # |
Pranlukast;103177-37-3
|
| PubChem CID |
11979774
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| Appearance |
White to off-white solid powder
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| LogP |
4.635
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
15
|
| Rotatable Bond Count |
18
|
| Heavy Atom Count |
73
|
| Complexity |
778
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
MSXTUBJFNBZPGC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/2C27H23N5O4.H2O/c2*33-23-17-24(26-29-31-32-30-26)36-25-21(23)10-6-11-22(25)28-27(34)19-12-14-20(15-13-19)35-16-5-4-9-18-7-2-1-3-8-18;/h2*1-3,6-8,10-15,17H,4-5,9,16H2,(H,28,34)(H,29,30,31,32);1H2
|
| Chemical Name |
N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]-4-(4-phenylbutoxy)benzamide;hydrate
|
| Synonyms |
pranlukast hydrate; FR702N558K; Benzamide, N-[4-oxo-2-(2H-tetrazol-5-yl)-4H-1-benzopyran-8-yl]-4-(4-phenylbutoxy)-, hydrate (2:1);
|
| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~50.97 mM)
H2O : ~1 mg/mL (~2.04 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.10 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0019 mL | 10.0096 mL | 20.0192 mL | |
| 5 mM | 0.4004 mL | 2.0019 mL | 4.0038 mL | |
| 10 mM | 0.2002 mL | 1.0010 mL | 2.0019 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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