Combinatorial approach to identification of tyrphostin inhibitors of cytokine signaling

Compound 5H4, a meta-trifluoromethyl derivative of tyrphostin AG490, was identified by screening a combinatorial library as a more potent inhibitor of JAK tyrosine kinase-dependent cell proliferation. The activity of 5H4 in cytokine-dependent cell lines and in lymphoma-prone IL-7 transgenic mice were examined.