Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530
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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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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”
From The molecular rationale of Src inhibition in colorectal carcinomas (2014) · cites this paper as [79]
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Cites
Tumour-cell invasion and migration: diversity and escape mechanisms
Friedl, P., & Wolf, K. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1075 · Cited by 3,225 · see citing works
Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome
Lozzio, C., & Lozzio, B. (1975) · Blood · doi:10.1182/blood.v45.3.321.bloodjournal453321 · Cited by 2,978 · see citing works
Cellular functions regulated by Src family kinases.
Thomas, S. M., & Brugge, J. (1997) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.13.1.513 · Cited by 2,610 · see citing works
The Conformational Plasticity of Protein Kinases
Huse, M., & Kuriyan, J. (2002) · Cell · doi:10.1016/s0092-8674(02)00741-9 · Cited by 1,760 · see citing works
Compensation mechanism in tumor cell migration
Wolf, K., Mazo, I. B., Leung, H. C. H., Engelke, K., von Andrian, U. H., Deryugina, E. I., Strongin, A. Y., Bröcker, E., & Friedl, P. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200209006 · Cited by 1,392 · see citing works
Lombardo, L. J., Lee, F. Y., Chen, P., Norris, D. J., Barrish, J. C., Behnia, K., Castaneda, S., Cornelius, L. A. M., Das, J., Doweyko, A. M., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049486a · Cited by 1,303 · see citing works
Protein Kinase Inhibitors: Insights into Drug Design from Structure
Noble, M. E. M., Endicott, J., & Johnson, L. N. (2004) · Science · doi:10.1126/science.1095920 · Cited by 1,207 · see citing works
Src family kinases in tumor progression and metastasis
Summy, J. M., & Gallick, G. E. (2003) · Cancer and Metastasis Reviews · doi:10.1023/a:1023772912750 · Cited by 827 · see citing works
Selective Requirement for Src Kinases during VEGF-Induced Angiogenesis and Vascular Permeability
Eliceiri, B. P., Paul, R., Schwartzberg, P. L., Hood, J. D., Leng, J., & Cheresh, D. A. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80221-x · Cited by 814 · see citing works
Wedge, S. R., Kendrew, J., Hennequin, L. F., Valentine, P. J., Barry, S. T., Brave, S. R., Smith, N. R., James, N. H., Dukes, M., Curwen, J., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4409 · Cited by 720 · see citing works
Self-citationSrc in cancer: deregulation and consequences for cell behaviour
Frame, M. C. (2002) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(02)00040-9 · Cited by 682 · see citing works
Kmiecik, T. E., & Shalloway, D. I. (1987) · Cell · doi:10.1016/0092-8674(87)90756-2 · Cited by 623 · see citing works
Martin, G. S. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35073094 · Cited by 599 · see citing works
The pharmacokinetics of Norpace.
Karim, A. (1975) · PubMed · Cited by 554 · see citing works
The interplay between Src and integrins in normal and tumor biology
Playford, M. P., & Schaller, M. D. (2004) · Oncogene · doi:10.1038/sj.onc.1208080 · Cited by 520 · see citing works
Activating SRC mutation in a subset of advanced human colon cancers
Irby, R. B., Mao, W., Coppola, D., Kang, J., Loubeau, J. M., Trudeau, W., Karl, R., Fujita, D. J., Jove, R., & Yeatman, T. J. (1999) · Nature Genetics · doi:10.1038/5971 · Cited by 489 · see citing works
Golas, J. M., Arndt, K. T., Etienne, C., Lucas, J., Nardin, D., Gibbons, J. J., Frost, P., Ye, F., Boschelli, D. H., & Boschelli, F. (2003) · PubMed · Cited by 412 · see citing works
Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer.
Talamonti, M. S., Roh, M. S., Curley, S. A., & Gallick, G. E. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116200 · Cited by 399 · see citing works
Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain
Cartwright, C. A., Eckhart, W., Simon, S., & Kaplan, P. L. (1987) · Cell · doi:10.1016/0092-8674(87)90758-6 · Cited by 390 · see citing works
p27 Phosphorylation by Src Regulates Inhibition of Cyclin E-Cdk2
Chu, I. M., Sun, J., Arnaout, A., Kahn, H., Hanna, W. M., Narod, S. A., Sun, P., Tan, C., Hengst, L., & Slingerland, J. M. (2007) · Cell · doi:10.1016/j.cell.2006.11.049 · Cited by 372 · see citing works
Hennequin, L. F., Allen, J. M., Breed, J., Curwen, J., Fennell, M., Green, T. P., der Brempt, C. L., Morgentin, R., Norman, R. A., Olivier, A., et al. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060434q · Cited by 365 · see citing works
Self-citationSrc-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling
Avizienyte, E., Wyke, A. W., Jones, R. J., McLean, G. W., Westhoff, M., Brunton, V. G., & Frame, M. C. (2002) · Nature Cell Biology · doi:10.1038/ncb829 · Cited by 359 · see citing works
Wilkinson, R. W., Odedra, R., Heaton, S. P., Wedge, S. R., Keen, N., Crafter, C., Foster, J. R., Brady, M. C., Bigley, A. L., Brown, E., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2979 · Cited by 358 · see citing works
Self-citationChemical Inhibitors of Protein Kinases
Bridges, A. J. (2001) · Chemical Reviews · doi:10.1021/cr000250y · Cited by 321 · see citing works
Activation of pp60c-src protein kinase activity in human colon carcinoma.
Bolen, J. B., Veillette, A., Schwartz, A. M., DeSeau, V, & Rosen, N. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.8.2251 · Cited by 299 · see citing works
Hiscox, S., Morgan, L. D., Green, T. P., Barrow, D., Gee, J. M. W., & Nicholson, R. I. (2005) · Breast Cancer Research and Treatment · doi:10.1007/s10549-005-9120-9 · Cited by 274 · see citing works
Self-citationShor, A. C., Keschman, E. A., Lee, F. Y., Muro‐Cacho, C., Letson, G. D., Trent, J. C., Pledger, W. J., & Jove, R. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3469 · Cited by 234 · see citing works
Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues.
Rosen, N. X., Bolen, J. B., Schwartz, A. M., Cohen, P., DeSeau, V., & Israel, M. A. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)67084-x · Cited by 224 · see citing works
Trevino, J. G., Summy, J. M., Lesslie, D. P., Parikh, N. U., Hong, D. S., Lee, F. Y., Donato, N. J., Abbruzzese, J. L., Baker, C. H., & Gallick, G. E. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050570 · Cited by 206 · see citing works
Song, L., Morris, M. D., Bagui, T. K., Lee, F. Y., Jove, R., & Haura, E. B. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4620 · Cited by 203 · see citing works
Nam, J., Ino, Y., Sakamoto, M., & Hirohashi, S. (2002) · PubMed · Cited by 175 · see citing works
Mannervik, B. (1982) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(82)87023-7 · Cited by 173 · see citing works
Plé, P. A., Green, T. P., Hennequin, L. F., Curwen, J., Fennell, M., Allen, J. M., der Brempt, C. L., & Costello, G. F. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm030317k · Cited by 170 · see citing works
Self-citationVultur, A., Buettner, R., Kowolik, C. M., Liang, W. P., Smith, D. D., Boschelli, F., & Jove, R. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0126 · Cited by 170 · see citing works
Carragher, N. O., Walker, S. M., Carragher, L., Harris, F. M., Sawyer, T. K., Brunton, V., Ozanne, B. W., & Frame, M. C. (2006) · Oncogene · doi:10.1038/sj.onc.1209582 · Cited by 164 · see citing works
Self-citationManley, P. W., Cowan‐Jacob, S. W., & Mestan, J. (2005) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2005.07.040 · Cited by 160 · see citing works
Src and Ras are involved in separate pathways in epithelial cell scattering
Boyer, B., Roche, S., Denoyelle, M., & Thiery, J. P. (1997) · The EMBO Journal · doi:10.1093/emboj/16.19.5904 · Cited by 143 · see citing works
Self-citationKarlsson, R., Kullman-Magnusson, M., Hämäläinen, M., Remaeus, A., Andersson, K., Borg, P., Gyzander, E., & Deinum, J. (2000) · Analytical Biochemistry · doi:10.1006/abio.1999.4406 · Cited by 126 · see citing works
Serrels, A., Macpherson, I. R., Evans, T. R. J., Lee, F. Y., Clark, E. A., Sansom, O. J., Ashton, G. H. S., Frame, M. C., & Brunton, V. G. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0382 · Cited by 124 · see citing works
Irby, R., & Yeatman, T. J. (2002) · PubMed · Cited by 123 · see citing works
Src kinase contributes to the metastatic spread of carcinoma cells
Boyer, B., Bourgeois, Y., & Poupon, M. (2002) · Oncogene · doi:10.1038/sj.onc.1205298 · Cited by 118 · see citing works
Self-citationVallés, A. M., Beuvin, M., & Boyer, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405144200 · Cited by 93 · see citing works
Self-citationPrevention of MKK6-Dependent Activation by Binding to p38α MAP Kinase
Sullivan, J. E., Holdgate, G. A., Campbell, D., Timms, D. A., Gerhardt, S., Breed, J., Breeze, A. L., Bermingham, A., Pauptit, R. A., Norman, R. A., et al. (2005) · Biochemistry · doi:10.1021/bi051714v · Cited by 90 · see citing works
Self-citationJones, R. J., Avizienyte, E., Wyke, A. W., Owens, D. W., Brunton, V. G., & Frame, M. C. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600594 · Cited by 80 · see citing works
Emaduddin, M., Bicknell, D. C., Bodmer, W. F., & Feller, S. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712176105 · Cited by 50 · see citing works
Functional dissection of transformation by c‐Src and v‐Src
Oneyama, C., Hikita, T., Nada, S., & Okada, M. (2007) · Genes to Cells · doi:10.1111/j.1365-2443.2007.01145.x · Cited by 47 · see citing works
Targeting Protein Kinases for Bone Disease: Discovery and Development of Src Inhibitors
Metcalf, C. A., van Schravendijk, M. R., Dalgarno, D. C., & Sawyer, T. K. (2002) · Current Pharmaceutical Design · doi:10.2174/1381612023393323 · Cited by 45 · see citing works
Fu, Y.-N., Yeh, C.-L., Cheng, H., Yang, C.-H., Tsai, S. F., Huang, S.-F., & Chen, Y.-R. (2007) · Oncogene · doi:10.1038/sj.onc.1210684 · Cited by 37 · see citing works
The pyruvate kinase-coupled assay for ATPases: A critical analysis
Jenkins, W. T. (1991) · Analytical Biochemistry · doi:10.1016/0003-2697(91)90160-u · Cited by 27 · see citing works
Src Family Kinases as Regulators of Angiogenesis: Therapeutic Implications
Lesslie, D. P., & Gallick, G. E. (2005) · Current Cancer Therapy Reviews · doi:10.2174/1573394052952500 · Cited by 12 · see citing works
Phillips, K. A., Parikh, N. U., Kuwai, T., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.25.18_suppl.14032 · Cited by 5 · see citing works
Helfrich, B., Frederick, B. A., Raben, D., et al. (2006) · European Journal of Cancer Supplements · doi:10.1016/s1359-6349(06)70590-0 · Cited by 1 · see citing works
Phillips, K. A., Parikh, N. U., Park, S., et al. (2007) · Molecular Cancer Therapeutics · Cited by 1 · see citing works
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- 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
- PMC
- PMC5527863
- 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
- bronze
- doi.org
- 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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