Cancer and Infection Research Area, AstraZeneca, Alderley Park, Macclesfield Cheshire, SK10 4TG, UK.
Mol Oncol. 2009 Jun;3(3):248-61. doi: 10.1016/j.molonc.2009.01.002. Epub 2009 Feb 7.
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.
AZD0530 是一种口服 Src 抑制剂，在体外具有强大的抗迁移和抗侵袭作用，并在膀胱癌的小鼠模型中抑制转移。AZD0530 在体外对不同细胞系的增殖活性不同（IC（50）为 0.2 至 10μM）。AZD0530 抑制了 10 个异种移植模型中的 4 个肿瘤生长，并在生长抑制抵抗和敏感的异种移植中动态抑制Src 底物黏着斑激酶和桩蛋白的体内磷酸化。AZD0530 在 NBT-II 膀胱癌细胞中的活性与细胞迁移的抑制和细胞间黏附的稳定一致。这些数据表明 AZD0530 具有主要的抗侵袭药理学作用，可能限制多种癌症中的肿瘤进展。AZD0530 目前正在进行 II 期临床试验。
