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

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. (c) 2004 Wiley-Liss, Inc.