SKF-86002 dihydrochloride

SKF-86002 dihydrochloride用途

SKF-86002盐酸是一种口服活性p38 MAPK抑制剂,具有抗炎、抗关节炎和镇痛活性。SKF-86002盐酸抑制脂多糖(LPS)刺激的人单核细胞IL-1和TNF-α的产生(IC50=1μM)。SKF-86002盐酸抑制花生四烯酸的脂氧合酶和环氧合酶介导的代谢[1][2][3]。

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SKF-86002 dihydrochloride名称

[ CAS 号 ]:
116339-68-5

[ 英文名 ]:
SKF 86002 dihydrochloride

[英文别名 ]:

SKF-86002 dihydrochloride生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> MAPK/ERK信号通路 >> p38 MAPK

研究领域 >> 炎症/免疫

[体外研究]

SKF-86002二盐酸盐(10μM；1小时)抑制紫外线照射(UV)应激刺激诱导的细胞凋亡[1]。SKF-86002二盐酸盐不抑制紫外线诱导的未分化HL-60细胞凋亡[1]。SKF-86002二氢氯化物(10μM；72小时)阻止IL-4诱导的单核细胞或U937细胞CD23表面表达和蛋白质形成,对CD23 mRNA水平没有影响[4]。Western Blot分析[4]细胞系：U937细胞浓度：10μM培养时间：72小时结果：IL-4处理的U937细胞上CD23水平降低。

[体内研究]

SKF-86002二氢氯化物(10-90 mg/kg；p.o.；每日；持续22天)具有抗关节炎活性[5]。动物模型：Lewis大鼠,佐剂性关节炎(AA)[5]剂量：10 mg/kg、30 mg/kg、90 mg/kg给药：口服,每日,持续22天结果：注射佐剂后后腿体积显著减少。

[参考文献]

[1]. Frasch SC, et al. p38 mitogen-activated protein kinase-dependent and -independent intracellular signal transduction pathways leading to apoptosis in human neutrophils. J Biol Chem. 1998 Apr 3;273(14):8389-97.

[2]. Griswold DE, et al. SK&F 86002: a structurally novel anti-inflammatory agent that inhibits lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid. Biochem Pharmacol. 1987 Oct 15;36(20):3463-70.

[3]. Lee JC, et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature. 1994;372(6508):739-746.

[4]. L A Marshall, et al. Inhibitors of the p38 mitogen-activated kinase modulate IL-4 induction of low affinity IgE receptor (CD23) in human monocytes. J Immunol. 1998 Dec 1;161(11):6005-13.

[5]. M J DiMartino, et al. Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenase. Agents Actions. 1987 Feb;20(1-2):113-23.