本研究旨在按照新药申请的要求，概述聚乙二醇化重组人内皮素（M2ES）的临床前疗效和安全药理学。使用银染法评估了M2ES的纯度。采用Transwell细胞迁移实验检测M2ES的体外生物活性。在胰腺癌（Panc-1）和胃癌（MNK45）的裸鼠异种移植模型中评估了M2ES的抗肿瘤疗效。对BALB/C小鼠进行不同剂量（6、12和24mg/kg）的静脉注射，监测药物给药前后的自主活动和合作睡眠。M2ES的明显分子量约为50 kDa，纯度大于98％。与对照组相比，M2ES明显抑制人体微血管内皮细胞（HMECs）的迁移。值得注意的是，每周给予M2ES的治疗显著提高了抗肿瘤效果。M2ES（24mg/kg或以下）的治疗对自主活动和催眠没有明显影响。基于M2ES的临床前疗效和安全药理学数据，M2ES可以被授权进行进一步的临床研究。版权所有© Bentham Science Publishers；如有任何查询，请发邮件到epub@benthamscience.net。

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.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. 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 microvascular endothelial cells (HMECs) cell 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.On the basis of the pre-clinical efficacy and safety pharmacology data of M2ES, M2ES can be authorized to carry out further clinical studies.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.