Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Stratowa, C. et al.

Stratowa, Baum, Castañon, Dahmann, Himmelsbach, Himmler, Loeber, Metz, Schnitzer, Solca, Spevak, Tontsch, von Rüden,

A comparative cell-based high throughput screening strategy for the discovery of selective tyrosine kinase inhibitors with anticancer activity.

Growth factor receptor tyrosine kinases (RTK) have been implicated in tumor growth, metastasis and angiogenesis, and are thus considered promising targets for therapeutic intervention in malignant diseases. We present a novel drug discovery strategy to find inhibitors of RTKs based on comparative screening of compound libraries employing functional cellular assays. Cell lines stably expressing HER2 and the receptors for hepatocyte growth factor ( HGF), vascular endothelial growth factor (VEGF), insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) have been established. All cell lines are based on FDC-P1, a murine myeloid progenitor cell line which allows a direct comparison of results obtained in primary screens. In addition, the same cell lines are suitable for compound optimization and for animal studies. Using this strategy we report the identification of promising lead candidates for further drug development which are highly selective, non-cytotoxic and cell permeable with potencies in the low micromolar range.[1]

References

A comparative cell-based high throughput screening strategy for the discovery of selective tyrosine kinase inhibitors with anticancer activity. Stratowa, C., Baum, A., Castañon, M.J., Dahmann, G., Himmelsbach, F., Himmler, A., Loeber, G., Metz, T., Schnitzer, R., Solca, F., Spevak, W., Tontsch, U., von Rüden, T. Anticancer Drug Des. (1999) [Pubmed]

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