Src family kinases as therapeutic targets

Despite significant efforts aimed at understanding and treating these diseases, current therapeutic options are still very limited because of major side effects and very high costs. Development of novel therapeutic strategies for the treatment of chronic autoimmune and inflammatory diseases is therefore a highly important research priority.

Src family kinases are nonreceptor tyrosine kinases involved in diverse biological functions. Their role in cellular proliferation and invasion, the high frequency of activating mutations in Src family kinase genes in tumours and the presence of oncogenic variants in oncogenic viruses indicated a role for these kinases in malignancies.

Those findings also triggered significant efforts aimed at therapeutic targeting of Src family kinases in human cancer, and resulted in the development of several small molecule Src family kinase inhibitors that showed a very positive effect in oncology patients during the last several years. Src family kinases are also involved in various functions of immune cells, but their role in inflammatory diseases and the possibility of their therapeutic targeting in those diseases have not yet been widely appreciated.

TARKINAID aims to develop novel small molecule anti inflammatory compounds based on the inhibition of Src family kinases in inflammatory cells. The core part of the project is the preclinical analysis of novel Src family kinase inhibitors in various animal models of chronic autoimmune and inflammatory diseases.

That core part is supported and preceded by a series of in vitro and additional initial in vivo assays, to predict and optimise the most promising inhibitors and to test their safety and pharmacokinetic characteristics.

Preliminary studies performed by consortium members clearly indicate a previously unappreciated and mostly unanticipated role of Src family kinases in various aspects of autoimmune inflammatory diseases. These observations suggest that the kinases may be suitable therapeutic targets for the therapy of chronic autoimmune and inflammatory diseases.

The consortium has already developed and selected a significant number of novel compounds that may serve as suitable early lead molecules for the development of anti inflammatory drugs based on pharmacological inhibition of Src family kinases. It has also developed a large number of in vitro and in vivo model systems to test various aspects of autoimmune inflammatory processes.

The fact that the initial studies on the role of Src family kinases in inflammatory diseases and the initial selection of the above compounds have not yet been published provides a major competitive advantage for the consortium during the development of Src family targeted anti inflammatory therapeutics.