YM-976

PDE4抑制剂（对人类外周白细胞酶的IC50=2.2nM）；对PDE4的选择性优于PDE1、-2、-3和-5（所有IC50s=>3µM）；抑制人类PBMCs中LPS诱导的TNF-α产生；抑制大鼠胸膜炎模型中角叉菜胶诱导的胸腔细胞浸润（ED30=9.1mg/kg）；抑制大鼠、小鼠和雪貂中抗原诱导的肺嗜酸性粒细胞浸润（ED50s分别为1.7、5.8和1.2mg/kg）；剂量高达10mg/kg时不会引起雪貂呕吐；减少豚鼠哮喘模型中卵清蛋白引起的支气管收缩，以及气道血浆渗漏、嗜酸性粒细胞浸润和高反应性（ED50s分别为7.3、5.7、1和0.52mg/kg）；减少豚鼠柠檬酸引起的咳嗽。A PDE4 inhibitor (IC50 = 2.2 nM for the human peripheral leukocyte enzyme); selective for PDE4 over PDE1, -2, -3, and -5 (IC50s = >3 µM for all); inhibits LPS-induced TNF-α production in human PBMCs; inhibits carrageenan-induced pleural cavity cell infiltration in a rat model of pleurisy (ED30 = 9.1 mg/kg); inhibits antigen-induced lung eosinophil infiltration in rats, mice, and ferrets (ED50s = 1.7, 5.8, and 1.2 mg/kg, respectively); does not induce emesis in ferrets at doses up to 10 mg/kg; reduces ovalbumin-induced bronchoconstriction, as well as airway plasma leakage, eosinophil infiltration, and hyperreactivity in a guinea pig model of asthma (ED50s = 7.3, 5.7, 1, and 0.52 mg/kg, respectively); reduces citric acid-induced cough in guinea pigs.