Data from OSI-930: A Novel Selective Inhibitor of Kit and Kinase Insert Domain Receptor Tyrosine Kinases with Antitumor Activity in Mouse Xenograft Models

• DOI: 10.1158/0008-5472.c.6495345
• Publication Date: 2023-03-30T21:07:47Z
• Authors: Andrew J. Garton; Andrew P.A. Crew; Maryland Franklin; Andrew R. Cooke; Graham M. Wynne; Linda Castaldo; Jennifer Kahler; Shannon L. Winski; April Franks; Eric N. Brown; Mark A. Bittner; John F. Keily; Paul Briner; Chris Hidden; Mary C. Srebernak; Carrie Pirrit; Matthew O'Connor; Anna Chan; Bojana Vulevic; Dwight Henninger; Karen Hart; Regina Sennello; An-Hu Li; Tao Zhang; Frank Richardson; David L. Emerson; Arlindo L. Castel...; Lee D. Arnold; Neil W. Gibson

<div>Abstract<p>OSI-930 is a novel inhibitor of the receptor tyrosine kinases Kit and kinase insert domain (KDR), which currently being evaluated in clinical studies. OSI-930 selectively inhibits KDR with similar potency intact cells also these targets <i>in vivo</i> following oral dosing. We have investigated relationships between observed cell-based assays vitro</i>, plasma exposure levels achieved dosing, time course target inhibition vivo</i>, antitumor activity tumor xenograft models. In mutant Kit–expressing HMC-1 model, prolonged was at doses 10 50 mg/kg this dose range associated activity. Similarly, wild-type NCI-H526 model 100 to 200 mg/kg, level significant as well majority other models tested. The data suggest that mouse maintain molecular for period. Furthermore, pharmacokinetic evaluation effective provides an estimate concentrations may be required achieve humans would therefore expected yield therapeutic benefit future evaluations OSI-930. (Cancer Res 2006; 66(2): 1015-24)</p></div>