Despite significant efforts, autoimmune and chronic inflammatory disorders such as rheumatoid arthritis pose a heavy socioeconomic burden. Current therapeutic options are still very limited and have major side effects, highlighting the imminent need for novel therapeutic strategies. Towards this goal, the EU-funded TARKINAID (Targeting Src-family tyrosine kinases in chronic autoimmune and inflammatory diseases) project turned to inhibitors of the Src-family kinases, which are known for their involvement in tumour development and progression. Src kinases are also present in immune cells and preliminary findings in experimental animals suggest they could be implicated in the development of inflammatory diseases. Researchers identified a number of small molecule Src inhibitors with anti-inflammatory properties and developed a set of structurally related drug candidates. These proved to be functional in vitro, inhibiting immune cell activation and reducing inflammatory responses at a greater extent than the known tyrosine kinase inhibitor, dasatinib. This demonstrated the therapeutic value of these candidates for future utilisation in clinical drug development. Furthermore, scientists demonstrated novel effects of the anti-leukaemic agent dasatinib in various inflammatory disease models. This included attenuation of immune complex-induced arthritis and protection from lung damage in acute lung injury and allergic asthma. The consortium also investigated novel functions of the myeloid Src-family kinases – Hck, Fgr and Lyn in inflammatory disorders. Their efforts unveiled important mechanistic insight and identified several other components in the downstream signalling pathway of these kinases. Taken together, the activities of the TARKINAID project proposed new therapeutic approaches in chronic inflammatory and autoimmune diseases. These novel Src kinase inhibitors could be used as oral anti-inflammatory agents and will be submitted for patent applications. Finally, a better understanding of autoimmune and inflammatory disease pathogenesis will lead to better diagnosis and therapeutic approaches in the future.
Non-steroid anti-inflammatory drugs, autoimmune, rheumatoid arthritis, inhibitor, Src kinase, dasatinib