CGS 8515作为一种选择性5-脂氧合酶（5-LO）抑制剂的特性

Characterization of CGS 8515 as a selective 5-lipoxygenase (5-LO) inhibitor.

Ku E C, Raychaudhuri A, Ghai G, Kimble E F, Lee W H, Colombo C, Dotson R, White D, Oglesby T D, Wasley J W

CIBA-GEIGY Corp., Summit, New Jersey 07901.

Adv Prostaglandin Thromboxane Leukot Res. 1989;19:86-9.

Abstract

CGS 8515 selectively inhibited 5-LO (IC50 = 0.1 microM) with negligible effect on CO, 12-LO, 15-LO and TxS at concentrations up to 100 microM. 2. CGS 8515 selectively inhibited A23187-induced formation of 5-LO products in rat and human whole blood with a 20-70 fold separation of effects over the formation of CO products. 3. Ex vivo and in vivo studies with rats showed that CGS 8515, at an oral dose of 2-50 mg/kg, significantly inhibited A23187-induced formation of LTs in whole blood and in the lung. The effect persisted for at least 6 h in the ex vivo blood model. 4. CGS 8515, at oral doses as low as 5 mg/kg, significantly suppressed exudate volume and leukocyte migration in the carrageenan-induced pleurisy and sponge models in the rat.

摘要

CGS 8515可选择性抑制5-脂氧合酶（IC50 = 0.1微摩尔），在浓度高达100微摩尔时，对环氧化酶、12-脂氧合酶、15-脂氧合酶和血栓素合成酶的影响可忽略不计。2. CGS 8515可选择性抑制A23187诱导的大鼠和人全血中5-脂氧合酶产物的形成，其对5-脂氧合酶产物形成的抑制作用与环氧化酶产物形成的抑制作用相比有20至70倍的差异。3. 对大鼠进行的体内外研究表明，口服剂量为2至50毫克/千克的CGS 8515可显著抑制A23187诱导的全血和肺中白三烯的形成。在体外血液模型中，该作用至少持续6小时。4. 口服剂量低至5毫克/千克的CGS 8515可显著抑制角叉菜胶诱导的大鼠胸膜炎和海绵模型中的渗出液体积和白细胞迁移。