Cited by 238Cancer Mechanisms and TherapyProtein Kinase Regulation and GTPase SignalingCancer Cells and Metastasis

Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530

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Green, Tim P., Fennell, Mike, Whittaker, Robin, Curwen, Jon, Jacobs, Vivien, Allen, Jack, Logie, Armelle, Hargreaves, Judith +12 more·2009·Molecular Oncology

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.

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Crossref · 10.1016/j.molonc.2009.01.002

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  • Saracatinib is an oral dual Src/Abl inhibitor targeting Csk and RTKs such as mutant EGFR; it shows anti-growth effects in several CRC cell lines in vitro and in mouse xenografts.

    “Saracatinib is also an oral dual Src/Abl inhibitor targeting Csk and RTKs, such as mutant forms of EGFR.Saracatinib shows anti-growth effects in several CRC cell lines in vitro and in mouse xenografts.79”

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  1. Green, T., Hennequin, L.F., Ple, P.A., Jones, R.J., Clack, G., Gallagher, N., 2005. Pre-clinical and early clinical activity of the highly selective, orally available, dual Src/Abl kinase inhibitor AZD0530. Proc. Am. Assoc. Cancer Res. 46 abst SY13-3.

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Authors
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.
Affiliations
  • AstraZeneca (United Kingdom) (GB)
  • Inserm (FR)
  • AstraZeneca (France) (FR)
Corresponding author
Green, Tim P.
Venue
Molecular Oncology
Publisher
Wiley
Published
2009-01-28
Volume
3
Issue
3
Pages
248-261
ISSN
  • 1574-7891 (ISSN-L)
  • 1878-0261
OpenAlex
W2160318185
Cited by
238
References
53
Citations by year
2026: 9 · 2025: 9 · 2024: 15 · 2023: 11 · 2022: 24 · 2021: 18 · 2020: 16 · 2019: 8 · 2018: 11 · 2017: 11 · 2016: 13 · 2015: 12 · 2014: 11 · 2013: 12 · 2012: 23
FWCI
13.62
Type
journal article
Language
en
Open access
Locations
  • Molecular Oncology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
AstraZeneca
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
AZD0530, Src kinase inhibitor, bladder cancer, metastasis, cell migration inhibition, tumor invasion, cell-cell adhesion, paxillin, focal adhesion kinase, xenograft models, antiproliferative activity
MeSH terms
Administration, Oral, Animals, Antineoplastic Agents, Urinary Bladder Neoplasms, Cell Movement, Humans, Mice, Nude, Neoplasm Invasiveness, Neoplasm Proteins, Neoplasm Transplantation, Phosphorylation, Quinazolines, Rats, Nude, Transplantation, Heterologous, Clinical Trials, Phase II as Topic, src-Family Kinases, Xenograft Model Antitumor Assays, NIH 3T3 Cells, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation, Mice, Rats, Focal Adhesion Kinase 1, Paxillin, Benzodioxoles

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