Development of Synthetic Aminopeptidase N/CD13 Inhibitors to Overcome Cancer Metastasis and Angiogenesis
Development of Synthetic Aminopeptidase N/CD13 Inhibitors to Overcome Cancer Metastasis and Angiogenesis
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DOI：
10.1021/ml3000758
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发表时间：
2012-12-01
影响因子：
4.2
通讯作者：
Xu, Wenfang
中科院分区：
文献类型：
--
作者：
Su, Li;Cao, Jiangying;Xu, Wenfang
癌症转移是其治疗的主要障碍，也是患者死亡的重要原因。抗转移药物有望为晚期转移性肿瘤患者带来希望。氨基肽酶N/CD13(APN)被认为是抗肿瘤转移和血管生成的重要靶点，但有关人工合成APN抑制剂的体内评价报道较少。在此，我们合成了一系列针对APN的化合物，并在体内外对其抗肿瘤转移和抗血管生成作用进行了评价。令人兴奋的是，化合物4m、4t和4cc具有最强的APN抑制活性，在体内外表现出显著的抗转移和抗血管生成作用，表明这些合成的APN抑制剂具有抑制肿瘤转移和血管生成的潜力。
Cancer metastasis is a major barrier to its treatment and an important cause of patient death. Antimetastatic agents hold promise for patients with advanced metastatic tumors. Aminopeptidase N/CD13 (APN) is being pursued by many as an important target against cancer metastasis and angiogenesis, but there are few reports on the in vivo evaluation of synthetic APN inhibitors. Herein, a series of compounds targeting APN were synthesized and evaluated for their antimetastasis and antiangiogenesis potency both in vitro and in vivo. Excitingly, compounds 4m, 4t, and 4cc, with the most potent APN inhibitory activities, displayed significant antimetastasis and antiangiogenesis effects in vitro and in vivo, suggesting that those synthetic APN inhibitors have the potential to overcome cancer metastasis and angiogenesis.