Inhibition of Protein-Tyrosine Kinases by Tyrphostins

This chapter discusses the inhibition of protein-tyrosine kinases by tyrphostins. Many protein tyrosine kinases (PTKs) catalyze the phosphorylation of tyrosine residues on exogenous substrates and the autophosphorylation of tyrosine residues. For testing the ability of PTKs to phosphorylate an exogenous substrate, synthetic copolymers of amino acids containing tyrosine residues are chosen as the substrate. Once the polymers are examined at three arbitrary concentrations, the concentration dependence of substrate phosphorylation is examined. Protein-tyrosine kinases can be inhibited both in vivo and in vitro by synthetic blockers, termed “tyrphostins.” This chapter describes the inhibition of in vitro phosphorylation and the antiproliferative activity of these compounds. It identifies representative PTK inhibitors that have been found to be potent blockers of EGF receptor kinase in vitro and inhibitors of EGF-dependcnt cell proliferation.