SMALL-MOLECULE INHIBITORS OF THE PLATELET-DERIVED GROWTH-FACTOR RECEPTOR, THE FIBROBLAST GROWTH-FACTOR RECEPTOR, AND SRC FAMILY TYROSINE KINASES

The inhibition of tyrosine kinases involved in growth factor signal tr ansduction pathways represents an attractive strategy for controlling aberrant cellular growth. Over the last 4-5 years, there have been num erous reports on the discovery of small molecule inhibitors for potent ial therapeutic applications to a number of proliferative diseases, pr incipally cancer and restenosis, where the over-expression of certain tyrosine kinases has been demonstrated. These include, amongst others, the platelet-derived growth factor receptor, the fibroblast growth fa ctor receptor, and the nonreceptor c-Src tyrosine kinase. This review compiles published reports and patent filings from 1995 to mid-1997 th at include data directly related to inhibition of the platelet-derived growth factor receptor, fibroblast growth factor receptor, and Src fa mily tyrosine kinases. Potential clinical applications for selected cl asses of tyrosine kinase inhibitors reviewed herein will likely depend on the demonstration of meaningful activity in a variety of therapeut ic targets in animal models. (C) 1997 Elsevier Science Inc.