Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor - Study of Lck- and FynT-dependent T cell activation

Here, we have studied the activity of a novel protein-tyrosine kinase inhibitor that is selective for the Src family of tyrosine kinases, We have focused our study on the effects of this compound on T cell receptor-induced T cell activation, a process dependent on the activity of the Src kinases Lck and FynT. This compound is a nanomolar inhibitor of Lck and FynT, inhibits anti-CDS-induced protein-tyrosine kinase activity in T cells, demonstrates selectivity for Lck and FynT over ZAP-70, and preferentially inhibits T cell receptor-dependent anti-CD3-induced T cell proliferation over non-T cell receptor-dependent phorbol 12-myristate 13-acetate/interleukin-2 (IL-S) induced T cell proliferation, Interestingly, this compound selectively inhibits the induction of the IL-2 gene, but not the granulocyte macrophage colony-stimulating factor or IL-2 receptor genes, This compound offers a useful new tool for examining the role of the Lck and FynT tyrosine kinases versus ZAP-70 in T cell. activation as well as the role of other Src family kinases in receptor function.