ML-221

APJ受体拮抗剂(IC50=4.8μM)；对APJ的选择性优于AT1(IC50=>78μM)；在cAMP和β-arrestin募集试验中拮抗apelin13诱导的APJ激活(IC50s分别为0.7和1.75μM)；抑制5-15μM的Mz-ChA-1胆管癌细胞增殖和血管生成；在150μg/kg剂量下减缓Mz-ChA-1小鼠异种移植模型中的肿瘤生长；在10μg/只动物剂量下减缓大鼠坐骨神经CCI诱导的机械性异常性疼痛和热痛觉过敏；在氧诱导性视网膜病变小鼠模型中抑制病理性血管生成并增强视网膜缺血区域的正常血管恢复。An APJ receptor antagonist (IC50 = 4.8 μM); selective for APJ over AT1 (IC50 = >78 μM); antagonizes apelin 13-induced activation of APJ in cAMP and β-arrestin recruitment assays (IC50s = 0.7 and 1.75 μM, respectively); inhibits proliferation and angiogenesis in Mz-ChA-1 cholangiocarcinoma cells from 5-15 μM; reduces tumor growth in a Mz-ChA-1 mouse xenograft model at 150 μg/kg; reduces sciatic CCI-induced mechanical allodynia and heat hyperalgesia in rats at 10 μg/animal; inhibits pathological angiogenesis and enhances normal vessel recovery in retinal ischemic regions in a mouse model of oxygen-induced retinopathy.