MAZ51, an indolinone that inhibits endothelial cell and tumor cell growth in vitro, suppresses tumor growth in vivo

Abstract We have recently described MAZ51, an indolinone that blocks the ligand‐induced autophosphorylation of VEGFR‐3, a receptor tyrosine kinase that plays a central role in the regulation of lymphangiogenesis. Here we show that MAZ51 is able to block the proliferation of VEGFR‐3‐expressing human endothelial cells and is less potently able to induce their apoptosis. MAZ51 also inhibits the proliferation and induces the apoptosis of a variety of non‐VEGFR‐3‐expressing tumor cell lines. These data suggest that MAZ51 blocks the activity of tyrosine kinases in addition to VEGFR‐3. In vivo , MAZ51 significantly inhibits the growth of rat mammary carcinomas. These data establish MAZ51 as a compound with antitumor properties that inhibits tumor growth directly and also indirectly by interfering with tumor‐host interactions. © 2004 Wiley‐Liss, Inc.