YLT192, a novel, orally active bioavailable inhibitor of VEGFR2 signaling with potent antiangiogenic activity and antitumor efficacy in preclinical models.

ABSTRACT: Antagonizing vascular endothelial growth factor receptor 2 (VEGFR2) to block angiogenesis has been applied toward cancer therapy for its role in promoting cancer growth and metastasis. However, most these clinical anticancer drugs have unexpected side effects. Development of novel VEGFR2 inhibitors with less toxicity remains an urgent need. In this study, we describe a novel, well-tolerated, and orally active VEGFR2 inhibitor, YLT192, which inhibits tumor angiogenesis and growth. YLT192 significantly inhibited kinase activity of VEGFR2 and suppressed proliferation, migration, invasion, and tube formation of human umbilical vascular endothelial cells (HUVEC) in vitro. In addition, it inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream signaling regulator in HUVEC. Zebrafish

SUBMITTER: Xia Y 

PROVIDER: S-EPMC4129416 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature