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SSR240612
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
SSR240612图片
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议

产品介绍
SSR240612 是一种有效的、具有口服活性的特异性非肽缓激肽 B1 受体拮抗剂,对人成纤维细胞 MRC5 和表达人 B1 受体的 HEK 细胞的 B1 激肽受体的 Kis 分别为 0.48 nM 和 0.73 nM,对 B2 受体的 Kis 分别为 481 nM 和 358 nM。豚鼠回肠膜和表达人B1受体的CHO细胞,分别。

Kinase experiment:

[3H]Lys0-des-Arg9-BK binding to cell membranes is performed in binding buffer of the following composition: 137 mM NaCl, 5.4 mM KCl, 1.05 mM MgCl2, 1.8 mM CaCl2, 1.2 mM NaH2PO4, 15.5 mM NaHCO3, 10 mM HEPES, 1 g/L bovine serum albumin (BSA), 140 mg/L bacitracin, and 1 μM captopril, pH 7.4. Membranes are incubated for 30 min at 25℃ in 500 μL of binding buffer containing 1 nM [3H]Lys0-des-Arg9-BK for competition curves or 0.1 to 10 nM for saturation isotherms. Filters are washed three times with 5 mL of binding buffer, and radioactivity is determined by liquid scintillation spectrometry. Nonspecific binding is determined by the addition of 1 μM of unlabeled Lys0-des-Arg9BK[1].

Animal experiment:

Mice[1]Groups of eight male albino mice under isoflurane anesthesia receive a 20-μL intraplantar injection into the right hind paw of 5 μg of IL-1β in phosphate-buffered saline/0.1% BSA. Forty minutes later (T = 0), mice under anesthesia receive a 20-μL intraplantar injection in the same paw of des-Arg9-BK (10 μg/paw) in water. SSR240612 or vehicle [5% (v/v) ethanol and 5% (v/v) Tween 80 in water] is administered by oral route at the doses of 1, 3, and 10 mg/kg 1 h before des-Arg9-BK injection and by intraperitoneal route at the doses of 0.1, 0.3, and 1 mg/kg 40 min before des-Arg9-BK injection. Paw volume is measured with a plethysmometer at T = -2 h (initial measurement) and at several times after edema induction (T = 20, 40, 60, and 120 min). Paw edema volume is expressed in milliliters as the difference between the paw volume at each time after edema induction and the initial paw volume. Results for each group are expressed as mean ± S.E.M. of individual paw edema volumes. Statistical analysis is performed after verification of normality and homogeneity of variances using repeated ANOVA, then Duncan's test, treated groups versus des-Arg9-BK control group[1].Rats[1]SSR240612 (suspended with 0.1% Tween 80 in saline) is administered by the oral route in a volume of 20 mL/kg, 2 h before the thermal hyperalgesia measurement. In the time course study, the compound is administered at 3 mg/kg p.o. 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h before measuring the withdrawal latencies in rats. Results are expressed in seconds as mean withdrawal latencies (s) ± S.E.M., and statistical analyses are performed using a two-way ANOVA followed by Dunnett's test[1].

产品描述

SSR240612 is a potent, and orally active specific non-peptide bradykinin B1 receptor antagonist, with Kis of 0.48 nM and 0.73 nM for B1 kinin receptors of human fibroblast MRC5 and HEK cells expressing human B1 receptors, 481 nM and 358 nM for B2 receptors of guinea pig ileum membranes and CHO cells expressing human B1 receptor, respectively.

SSR240612 is a potent bradykinin B1 receptor antagonist, with Kis of 0.48 nM and 0.73 nM for B2 kinin receptors of human fibroblast MRC5 and HEK cells expressing human B1 receptors, 481 nM and 358 nM for B1 receptors of guinea pig ileum membranes and CHO cells expressing human B1 receptor, respectively. SSR240612 inhibits inositol phosphate 1 formation with an IC50 of 1.9 nM, but shows no obvious effect on inositol phosphate-1 formation induced by BK (3 nM) activation of B2 receptor in human fibroblast MRC5[1].

SSR240612 (10 mg/kg p.o. or 0.3, 1 mg/kg i.p.) obviously blocks the des-Arg9-BK-induced paw edema in the mice. SSR240612 (10 and 30 mg/kg) reduces the duration of the late phase of paw licking in a dose dependent manner in the formalin model of inflammation in mice. SSR240612 (0.3, 3, and 30 mg/kg, p.o.) treatment before capsaicin potently and non-concentration-dependently reduces the ear edema. SSR240612 (0.3 mg/kg, i.v.) also suppresses the tissue destruction and neutrophil accumulation in the rat intestine, after splanchnic artery occlusion/reperfusion. Moreover, SSR240612 (1 and 3 mg/kg p.o.) dramacally increases the withdrawal latencies in the thermal hyperalgesia induced by UV irradiation in rats[1]. SSR240612 inhibits tactile and cold allodynia at 3 h in glucose-fed rats but had no effect in control rats with ID50s of 5.5 and 7.1 mg/kg, respectively. SSR240612 shows no effect on plasma glucose and insulin, insulin resistance (HOMA index) and aortic superoxide anion production in glucose-fed rats at 10 mg/kg[2].

References:
[1]. Gougat J, et al. SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization. J Pharmacol Exp Ther. 2004 May;309(2):661-9.
[2]. Dias JP, et al. The kinin B1 receptor antagonist SSR240612 reverses tactile and cold allodynia in an experimental rat model of insulin resistance. Br J Pharmacol. 2007 Sep;152(2):280-7. Epub 2007 Jul 9.