Open AccessPreclinical anticancer activity of the potent, oral Src inhibitor AZD0530
Author(s) -
Green Tim P.,
Fennell Mike,
Whittaker Robin,
Curwen Jon,
Jacobs Vivien,
Allen Jack,
Logie Armelle,
Hargreaves Judith,
Hickinson D. Mark,
Wilkinson Robert W.,
Elvin Paul,
Boyer Brigitte,
Carragher Neil,
Plé Patrick A.,
Bermingham Alun,
Holdgate Geoffrey A.,
Ward Walter H.J.,
Hennequin Laurent F.,
Davies Barry R.,
Costello Gerard F.
Publication year - 2009
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2009.01.002
Subject(s) - paxillin , cancer research , in vivo , in vitro , proto oncogene tyrosine protein kinase src , chemistry , cell growth , phosphorylation , pharmacology , cell , microbiology and biotechnology , cell adhesion , biology , biochemistry
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.