Introduction: This study aimed to outline the pre-clinical efficacy and safety pharmacology of PEGylated recombinant human endostatin (M2ES) according to the requirements of new drug application. Methods: The purity of M2ES was evaluated by using silver staining. Transwell migration assay was applied to detect the bioactivity of M2ES in vitro. The antitumor efficacy of M2ES was evaluated in an athymic nude mouse xenograft model of pancreatic cancer (Panc-1) and gastric cancer (MNK45). BALB/C mice were treated with different doses of M2ES (6, 12 and 24 mg/kg) intravenously, both autonomic activity and cooperative sleep were monitored before and after drug administration. Results: The apparent molecular weight of M2ES was about 50 kDa, and the purity was greater than 98%. Compared with the control group, M2ES significantly inhibits human micro-vascular endothelial cells (HMECs) migration in vitro. Notably, weekly administration of M2ES showed a significant antitumor efficacy when compared with the control group. Treatment of M2ES (24mg/kg or below) showed no obvious effect on both autonomic activity and hypnosis. Conclusion: On the basis of the pre-clinical efficacy and safety pharmacology data of M2ES, M2ES can be authorized to carry out further clinical studies.

中文翻译：

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聚乙二醇化重组人血管内皮抑素的临床前疗效和安全性药理学

简介：本研究旨在根据新药申报的要求，概述聚乙二醇化重组人内皮抑素（M2ES）的临床前疗效和安全性药理学。方法：采用银染法评价M2ES的纯度。采用Transwell迁移实验检测M2ES的体外生物活性。在胰腺癌（Panc-1）和胃癌（MNK45）的无胸腺裸鼠异种移植模型中评估了 M2ES 的抗肿瘤功效。BALB/C小鼠静脉注射不同剂量的M2ES（6、12和24 mg/kg），给药前后监测自主活动和合作睡眠。结果：M2ES的表观分子量约为50 kDa，纯度大于98%。与对照组相比，M2ES在体外显着抑制人微血管内皮细胞（HMEC）迁移。值得注意的是，与对照组相比，每周施用 M2ES 显示出显着的抗肿瘤功效。M2ES治疗（24mg/kg或以下）对自主活动和催眠没有明显影响。结论：基于M2ES的临床前疗效和安全性药理学数据，可以授权M2ES开展进一步的临床研究。