ABT-751

ABT-751 is an orally bioavailable tubulin inhibitor with IC50 of about 1.5 and 3.4 µM in neuroblastoma and non-neuroblastoma cell lines, respectively. ABT-751 had a broad spectrum of antitumor activity in a panel of 30 tumor cell lines in vitro and in xenograft models of human tumors in vivo, including gastric, colorectal, lung, and breast cancer models. ABT-751 showed antitumor activity against a broad spectrum of tumor lines including those resistant to conventional chemotherapies. A single dose of ABT-751 (30 mg/kg, intravenously) induced a rapid, transient reduction in tumor perfusion. After 1 h, tumor perfusion decreased by 57% before recovering to near pretreatment levels within 6 h. In contrast, ABT-751 produced little change in muscle perfusion at either time point. ABT-751, at concentrations corresponding to plasma levels achieved in vivo, caused endothelial cell retraction and significant loss of microtubules within 1 h.