Protein tyrosine kinases catalyze the transfer of phosphoryl groups from ATP to amino acids on proteins and play a fundamental role in signal transduction pathways in mammalian cells. In particular, Src and Src-family are non-receptor tyrosine kinases that regulate cell growth, differentiation, migration, adhesion and apoptosis. Src-family members share common features, with well defined domains. The activation of these enzymes in response to a variety of stimuli leads fi7om a close and inactive conformation to an open and active one, through a balance of phosphorylation and dephosphorylation of the enzyme structure, characterized in different cases by X-ray crystallography. Overexpression, deregulation or mutations of these enzymes have been observed and studied in many diseases, first of all in many human malignancies, such as colon, breast, pancreatic and other cancers. Src-family is also involved in other pathologic situations, such as osteoporosis, cardiovascular diseases, immune system disorders, and, recently, it has been also demonstrated the involvement of Src in prion diseases. Therefore, Src-family is an attractive and fundamental target for the design of new therapeutic agents against different pathologies, in particular cancer and bone diseases. Currently, there is no approved drug acting as Src kinase inhibitor, but new molecules, very potent and selective toward this family of kinases and also in vivo, are continuously synthesized, as demonstrated by the high number of publications and patents in this field. Here, we report several examples of Src kinase domain inhibitors, focusing our attention on chemical structures, structure-activity relationships and mechanism of action.

Schenone, S., Manetti, F., Botta, M. (2007). Synthetic Src-kinase domain inhibitors and their structural requirements. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 7(6), 660-680 [10.2174/187152007784111269].

Synthetic Src-kinase domain inhibitors and their structural requirements

MANETTI, FABRIZIO;BOTTA, MAURIZIO
2007-01-01

Abstract

Protein tyrosine kinases catalyze the transfer of phosphoryl groups from ATP to amino acids on proteins and play a fundamental role in signal transduction pathways in mammalian cells. In particular, Src and Src-family are non-receptor tyrosine kinases that regulate cell growth, differentiation, migration, adhesion and apoptosis. Src-family members share common features, with well defined domains. The activation of these enzymes in response to a variety of stimuli leads fi7om a close and inactive conformation to an open and active one, through a balance of phosphorylation and dephosphorylation of the enzyme structure, characterized in different cases by X-ray crystallography. Overexpression, deregulation or mutations of these enzymes have been observed and studied in many diseases, first of all in many human malignancies, such as colon, breast, pancreatic and other cancers. Src-family is also involved in other pathologic situations, such as osteoporosis, cardiovascular diseases, immune system disorders, and, recently, it has been also demonstrated the involvement of Src in prion diseases. Therefore, Src-family is an attractive and fundamental target for the design of new therapeutic agents against different pathologies, in particular cancer and bone diseases. Currently, there is no approved drug acting as Src kinase inhibitor, but new molecules, very potent and selective toward this family of kinases and also in vivo, are continuously synthesized, as demonstrated by the high number of publications and patents in this field. Here, we report several examples of Src kinase domain inhibitors, focusing our attention on chemical structures, structure-activity relationships and mechanism of action.
2007
Schenone, S., Manetti, F., Botta, M. (2007). Synthetic Src-kinase domain inhibitors and their structural requirements. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 7(6), 660-680 [10.2174/187152007784111269].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/22406
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