2. Academic Validation
  3. Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530

Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530

  • Mol Oncol. 2009 Jun;3(3):248-61. doi: 10.1016/j.molonc.2009.01.002.
Tim P Green 1,  Mike Fennell,  Robin Whittaker,  Jon Curwen,  Vivien Jacobs,  Jack Allen,  Armelle Logie,  Judith Hargreaves,  D Mark Hickinson,  Robert W Wilkinson,  Paul Elvin,  Brigitte Boyer,  Neil Carragher,  Patrick A Plé,  Alun Bermingham,  Geoffrey A Holdgate,  Walter H J Ward,  Laurent F Hennequin,  Barry R Davies,  Gerard F Costello
Affiliations

Affiliation

  • 1 Cancer and Infection Research Area, AstraZeneca, Alderley Park, Macclesfield Cheshire, SK10 4TG, UK. [email protected]
PMID: 19393585 DOI: 10.1016/j.molonc.2009.01.002
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 (IC(50) 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.

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