Novel Protein Kinase Inhibitors as New Therapeutics for Breast Cancer
Synthesis, Characterisation, Structure-Activity-Relationship, Biological Analysis and Application
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Breast cancer is the second most common cancer worldwide after lung cancer, the fifth most common cause of cancer death, and the leading cause of cancer death in women. Protein kinases regulate cellular proliferation and differentiation during development and homeostasis of normal tissues. Additionally, they are frequently overexpressed in cancers. As such, they have become promising targets for new therapies. Breast tumor kinase (Brk/PTK6), a non-receptor tyrosine kinase, as well as the Epidermal Growth Factor Receptors (EGFR), particularly HER2, were initially cloned from a metastatic breast...
Breast cancer is the second most common cancer worldwide after lung cancer, the fifth most common cause of cancer death, and the leading cause of cancer death in women. Protein kinases regulate cellular proliferation and differentiation during development and homeostasis of normal tissues. Additionally, they are frequently overexpressed in cancers. As such, they have become promising targets for new therapies. Breast tumor kinase (Brk/PTK6), a non-receptor tyrosine kinase, as well as the Epidermal Growth Factor Receptors (EGFR), particularly HER2, were initially cloned from a metastatic breast tumor, are overexpressed in 86 % and 30 % of human breast tumors and several breast cancer cell lines, respectively. Subsequently, targeting these two protein kinases is assumed to be of interest in breast cancer therapeutical survey. Novel -carboline derivatives have been synthesized and biologically investigated against both Brk and HER2 kinases which showed a very promising inhibitory profile in low nanomolar IC50 concentrations (e.g. 3 nM). Further NCI screenings exhibited a good cytostatic inhibitory profile for all tested compounds.
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