FPL 55712 (sodium salt)
目录号 : GC49696
A leukotriene receptor antagonist
Cas No.:40786-08-1
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
FPL 55712 (sodium salt) is a leukotriene (LT) receptor antagonist.1 It inhibits the binding of LTD4 to guinea pig lung homogenates (IC50 = 4 µM) and reduces LTD4-induced contraction of isolated guinea pig tracheal smooth muscle (pA2 = 1 µM). FPL 55712 (sodium salt) inhibits bronchoconstriction induced by LTD4, LTC4 , or LTE4 in guinea pigs (ID50s = 2, 6, and 1 mg/kg, respectively).
1.Cohen, N., Weber, G., Banner, B.L., et al.3,4-Dihydro-2H-1-benzopyran-2-carboxylic acids and related compounds as leukotriene antagonistsJ. Med. Chem.32(8)1842-1860(1989)
| Cas No. | 40786-08-1 | SDF | Download SDF |
| Canonical SMILES | O=C(C(OC1=C(CCC)C(OCC(COC2=C(CCC)C(O)=C(C(C)=O)C=C2)O)=CC=C13)=CC3=O)[O-].[Na+] | ||
| 分子式 | C27H29O9 • Na | 分子量 | 520.5 |
| 溶解度 | DMSO: soluble | 储存条件 | -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 | 1.9212 mL | 9.6061 mL | 19.2123 mL |
| 5 mM | 0.3842 mL | 1.9212 mL | 3.8425 mL |
| 10 mM | 0.1921 mL | 0.9606 mL | 1.9212 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。
MCI-826 is a potent and selective antagonist of peptide leukotrienes (p-LTs) and has characteristics distinctive from those of FPL 55712
Jpn J Pharmacol 1992 Sep;60(1):1-8.PMID:1460800DOI:10.1254/jjp.60.1.
Antagonistic effects of a newly synthesized compound, (E)-2,2-diethyl-3'-[2-[2-(4-isopropyl)thiazolyl]ethenyl]succinanilic+ ++ acid sodium salt (MCI-826) on the contraction of the isolated guinea pig trachea and human bronchus induced by various agonists including peptide leukotrienes (p-LTs), histamine, acetylcholine (ACh), prostaglandin (PG) D2 and others were investigated and compared with the effects of a p-LT antagonist, FPL 55712, in some experiments. MCI-826 potently antagonized LTD4- and LTE4-induced contractions at extremely low concentrations in the isolated guinea pig trachea with pA2 values of 8.3 and 8.9, respectively, on a molar basis. These values indicated that MCI-826 is over 100 times stronger than FPL 55712. Similarly, MCI-826 at 10(-8) g/ml (2.4 x 10(-8) M) markedly antagonized LTD4-induced contractions of the isolated human bronchus. Although FPL 55712 fairly inhibited the 10(-9) g/ml LTC4-induced contraction of the isolated guinea pig trachea, MCI-826 had little effect on the contraction at high concentrations like 3 x 10(-6) g/ml (7.1 x 10(-6) M). MCI-826 modestly affected the other agonist-induced contractions and the resting tonus of the isolated guinea pig trachea at 10(-6) g/ml (2.4 x 10(-6) M) or higher concentrations, but FPL 55712 caused fair inhibition of some of those contractions and gradually lowered the resting tonus with time. These results indicate that MCI-826 is a highly potent and selective antagonist of LTD4 and LTE4 and can be a useful tool for biological and pharmacological experiments on p-LTs.
Protein kinase C and tracheal contraction at low temperature
J Pharmacol Exp Ther 1987 Oct;243(1):270-80.PMID:3668858doi
During exercise or dry air-induced asthma, airway walls cool. However, the role of temperature in the regulation of airway tone is not clear. Protein kinase C (PKC) is an important second messenger in the mediation of cell responses. To explore whether changes in temperature affect pathways involving PKC in airways, we examined the effects of phorbol esters, potent activators of PKC, in guinea pig tracheal rings at various temperatures. Phorbol-12,13-diacetate (PDA) caused a reduction in tracheal tone at 37 degrees C and an increase in tone when temperature was reduced to 22 degrees C. Increases in tone were also produced by PDA when cell membranes were depolarized by ouabain (10 microM) or KCl (30 mM) at 37 degrees C. Contractions produced by PDA at 22 degrees C were inhibited by lipoxygenase inhibitors [ETYA (5,8,11,14-eicosatetraynoic acid), NDGA (nordihydroguaiaretic acid) and phenidone] and a leukotriene receptor antagonist [FPL 55712 (sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxyl] -4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate)]. Contractions produced by PDA at 37 degrees C or 22 degrees C in the presence of ouabain (10 mM) or KCl (30 mM) were not affected by these drugs. These results indicate that changes in temperature have profound effects on responses resulting from PKC activation. At low temperature, the lipoxygenase pathway mediates responses. Thus, cooling has the potential to modify a major intracellular pathway regulating physiological responses of the airways.
The effects of antiallergic and bronchodilator drugs on platelet-activating factor (PAF-acether) induced bronchospasm and platelet aggregation
Agents Actions 1984 Dec;15(5-6):636-42.PMID:6152379DOI:10.1007/BF01966785.
Platelet activating factor (PAF-acether) is a potential mediator of asthma and inflammation. Recently, the suggestion was made that inhibition of PAF-acether by disodium cromoglycate (DSCG) might be partly responsible for the effectiveness of DSCG in asthma. We have extended these studies and examined the effects of antiallergic and bronchodilator drugs on PAF-acether induced bronchospasm after i.v. administration in guinea pigs and in vitro platelet aggregation in rabbits. Neither DSCG nor Wy-41,195, a potent orally effective antiallergic, altered either of the PAF-acether responses. Furthermore, aerosolized ipratropium, promethazine, ketotifen and FPL 55712 failed to affect the PAF-acether-induced bronchospasm. The same drugs were also ineffective against platelet aggregation induced by PAF-acether. In contrast, aerosolized thiazinamium chloride inhibited the bronchospasm and also inhibited PAF-acether-induced platelet aggregation. Thiazinamium chloride possessed weak antiaggregatory effects against ADP and was without effect against arachidonic acid-induced platelet aggregation. Both lipoxygenase and cyclooxygenase products of arachidonic acid metabolism appear to be involved in PAF-acether bronchospasm since i.v. administered lipoxygenase inhibitors (phenidone, BW755c and NDGA) and indomethacin independently inhibited this in vivo response. However, these drugs failed to alter platelet aggregation to PAF-acether. Thiazinamium chloride may be capable of directly antagonizing the PAF-acether-induced platelet aggregatory response and, in addition, inhibiting the synthesis and/or effects of bronchoconstrictor amines and endogenously generated arachidonic acid metabolites.
Effects of hyperosmolarity on human isolated central airways
Br J Pharmacol 1991 Apr;102(4):931-7.PMID:1855121DOI:10.1111/j.1476-5381.1991.tb12279.x.
1. We studied the effect of hyperosmolarity on human isolated airways because a better understanding of the effect of hyperosmolarity on the human airway wall may improve insight into the pathophysiology of hyperosmolarity-induced bronchoconstriction in asthma. 2. In cartilaginous bronchial rings dissected from fresh human lung tissue, hyperosmolar krebs-Henseleit buffer (450 mosM, extra sodium chloride added) evoked a biphasic response: a rapid relaxation phase (peak after 5.0 +/- 0.3 min) followed by a slow contraction phase (peak after 25.4 +/- 0.8 min). 3. With the histamine (H1) receptor antagonist mepyramine, the contraction phase was reduced to 41.2% of the control value (P less than 0.001), with atropine to 50.0% (P less than 0.01), with the local anaesthetic lignocaine to 48.7% (P less than 0.05) and with mepyramine together with atropine to 19.2% (P less than 0.001). 4. With the inhibitor of neutral metalloendopeptidase, phosphoramidon, the contraction phase increased to 128.0% of the control value (P less than 0.05) and after removal of the epithelium to 131.8% (P less than 0.05). 5. Indomethacin, the leukotriene C4/D4 (LTC4/D4) antagonist FPL 55712 or the blocker of nerve conduction, tetrodotoxin, had no effect on the contractile phase. 6. The relaxation phase was not altered by any of these drugs nor by epithelial denudation. The relaxation phase was also unchanged in the presence of alpha-chymotrypsin, which degrades muscle relaxing peptides such as vasoactive intestinal peptide. 7. Hyperosmolar buffer slightly increased the sensitivity and maximal response to methacholine as well as the cholinergic twitch to electric field stimulation. 8. We conclude that hyperosmolarity releases acetylcholine, histamine and neuropeptides in the human airway wall in sufficient quantities to contract airway smooth muscle. This release itself or its effect on airway muscle is modulated by the airway epithelium. The mechanism of the relaxation phase may be an unknown smooth muscle relaxing substance or a direct effect on the airway muscle, related to ion fluxes.
Characterization of the leukotriene D4 receptor in guinea-pig lung
Eur J Pharmacol 1984 Jun 15;102(1):1-11.PMID:6090152DOI:10.1016/0014-2999(84)90331-5.
The effects of monovalent, divalent cations, buffere species and pH dependency on [3H]leukotriene D4 binding to the receptor have been characterized in vitro by using a radioligand binding assay. It was found that Ca2+, Mg2+, Co2+ and Mn2+ enhanced the specific binding. High concentrations of NaCl (150-300 mM) inhibited the specific binding to the receptor. The specific binding was also found to be higher in Pipes buffer (pH 6.5) than in Tris, Hepes and phosphate buffer at pH 7.0-8.0. Conversion of [3H]leukotriene D4 was minimized by inclusion of 1 mM cysteine, glycine in the incubation buffer and maintaining the temperature at 22 degrees C. Under the conditions employed, the dissociation constant (KD) and the receptor density (Bmax) were calculated to be 1.8 +/- 0.9 nM and 2100 +/- 375 fmol/mg protein respectively. The leukotriene antagonist FPL 55712, agonist 5R, 6S-LTD4 and LTE4 competed with the [3H]LTD4 binding to the receptor. Prostaglandins, alpha-, beta-adrenergic and dopaminergic receptor agonists and antagonists did not compete significantly.