[Recent advances in development of antitumor tyrosine kinase inhibitors]

Abstract

Protein tyrosine kinases are critical enzymes in regulating cellular growth and differentiation and are also deeply involved in oncogenesis since they are frequently activated in a variety of human cancers. Novel compounds that inhibit epidermal growth factor receptors (EGF-R) with high specificity and potency were developed, and their antitumor effects on EGF-R overexpressing cells and in vivo tumor models were demonstrated. Novel compounds that preferentially inhibit human glioma cells expressing truncated rather than wild-type EGF-R were also developed. Tyrphostin analogs which inhibit angiogenesis and thereby suppress tumor cell growth were also identified by screening inhibitors of Flk-1 tyrosine kinase.