Development of Synthetic Aminopeptidase N/CD13 Inhibitors to Overcome Cancer Metastasis and Angiogenesis

Abstract

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 <i>in vivo</i> evaluation of synthetic APN inhibitors. Herein, a series of compounds targeting APN were synthesized and evaluated for their antimetastasis and antiangiogenesis potency both <i>in vitro</i> and <i>in vivo</i>. Excitingly, compounds <b>4m</b>, <b>4t</b>, and <b>4cc</b>, with the most potent APN inhibitory activities, displayed significant antimetastasis and antiangiogenesis effects <i>in vitro</i> and <i>in vivo</i>, suggesting that those synthetic APN inhibitors have the potential to overcome cancer metastasis and angiogenesis