Receptor (RTK) and nonreceptor (NTK) protein tyrosine kinases play a central role in trans- duction of extracellular signals, both in normal and neoplastic cells. Therefore, several approaches to inhibit PTKs have been developed. According to the structure of natural protein kinase inhibitors (quer- cetin, erbstatin ) Levitzki and coworkers prepared first synthetic tyrosine kinase inhibitors and coined the term tyrphostins (tyrosine phosphorylation inhibitors). Over 30 tyrphostins are now in various stages of clinical development.
One of the major areas of activity of growth factors belonging to the EGF family is the regulation of growth and differentiation of epidermal cells and epithelial cells. Interactions of the EGF-like polypeptides and their receptor (ErbB) are the subject of a vast number of works published in the last decade. However, even the latest reports do not settle definitively that EGF-related factors are physiologically relevant and what is the mechanism for regulating growth, differentiation and programmed cell death of keratinocytes.