Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530

Abstract

AZD0530, an orally available Src inhibitor, demonstrated potent antimigratory and anti‐invasive 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 –>10μM). 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.