Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530
| Autor: | Robin D. Whittaker, Geoffrey A. Holdgate, Vivien Jacobs, M. Fennell, Laurent Francois Andre Hennequin, Judith A. Hargreaves, Brigitte Boyer, Alun Bermingham, Tim P. Green, Jon Curwen, Walter H.J. Ward, Allen Jack Mcqueen, Paul Elvin, Robert W. Wilkinson, Gerard Costello, Patrick Ple, Neil O. Carragher, D. Mark Hickinson, Barry R. Davies, Armelle Logie |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Transplantation Heterologous Administration Oral Mice Nude Antineoplastic Agents Pharmacology Metastasis Mice Rats Nude Clinical Trials Phase II as Topic In vivo Cell Movement Cell Line Tumor Genetics medicine Animals Humans Neoplasm Invasiveness Benzodioxoles Phosphorylation Protein Kinase Inhibitors Paxillin Cell Proliferation biology Cell migration General Medicine medicine.disease Xenograft Model Antitumor Assays In vitro Neoplasm Proteins Rats Transplantation src-Family Kinases Oncology Urinary Bladder Neoplasms Tumor progression Focal Adhesion Kinase 1 Papers biology.protein NIH 3T3 Cells Quinazolines Molecular Medicine Neoplasm Transplantation Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Green, T P, Fennell, M, Whittaker, R, Curwen, J, Jacobs, V, Allen, J, Logie, A, Hargreaves, J, Hickinson, D M, Wilkinson, R W, Elvin, P, Boyer, B, Carragher, N, Plé, P A, Bermingham, A, Holdgate, G A, Ward, W H J, Hennequin, L F, Davies, B R & Costello, G F 2009, ' Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530 ', Molecular Oncology, vol. 3, no. 3, pp. 248-261 . https://doi.org/10.1016/j.molonc.2009.01.002 |
| DOI: | 10.1016/j.molonc.2009.01.002 |
| Popis: | 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 –> 10 μM). 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. |
| Databáze: | OpenAIRE |
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