Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530

AZD0530, an orally available Src inhibitor, demonstrated potent antimigratory and antiinvasive effects in vitro, and inhibited metastasis in a murine model of bladder cancer. Antiproliferative activity of AZD0530 in Vitro varied between cell lines (IC50 0.2 -> 10 mu M). AZD0530 inhibited tumor growth in 4/10 xenograft models tested and dynamically inhibited in vivo phosphorylation of Src substrates paxillin and FAK in both growth-inhibition-resistant and -sensitive xenografts. The activity of AZD0530 in NBT-II bladder cancer cells in vitro was consistent with inhibition of cell migration and stabilization of cell-cell adhesion. These data suggest a dominant anti-invasive pharmacology for AZD0530 that may limit tumor progression in a range of cancers. AZD0530 is currently in Phase II clinical trials. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.