Semaxanib is a potent and selective vascular endothelial growth factor (VEGF) receptor protein tyrosine kinase 1/2 inhibitor that also inhibits other tyrosine kinases KIT, MET, FLT3, and RET. Semaxanib inhibited cell migration of human vascular endothelial cells expressing both Flt-1 and KDR in response to VEGF and also inhibited the cell migration in response to placenta growth factor (PIGF), a specific ligand for Flt-1. Chemotaxis of monocytes expressing only Flt-1 was also inhibited by SU5416 in a dose-dependent manner. Semaxanib targets the VEGF pathway, and both in vivo and in vitro studies have demonstrated antiangiogenic potential. On February 2002, Pharmacia, the then-parent of Sugen, prematurely ended Phase III clinical trials of Semaxinib in the treatment of advanced colorectal cancer due to discouraging results.

GZD824 is a novel orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50 of 0.34 nM and 0.68 nM, respectively. In vivo efficacy studies in mouse xenograft or allograft models of human leukemia demonstrated that GZD824 successfully suppressed the growth of tumors driven by native Bcr-Abl, Bcr-Abl T315I, Bcr-Abl G250E, Bcr-Abl Q252H, Bcr-Abl E255K and Bcr-Abl F317L. GZD824 also provided a significant survival benefit leukemia model mice allografted with luciferase-expressing Ba/F3 cells driven by the mutant Bcr-Abl T315I kinase. The potential for compound GZD824 to overcome all of the Bcr-Abl mutations that result in clinically acquired resistance to imatinib indicates that this novel Bcr-Abl inhibitor is a promising lead candidate for further development. GZD824 has also being shown to suppresses pre-B ALL cells through inhibition of the SRC kinase and PI3K/AKT pathways and may be a potential therapeutic agent for the management of pre-B ALL.