Editorial Oncologic, Endocrine & Metabolic: The current status of tyrosine kinase inhibitors: Do the diarylamine inhibitors of the EGF receptor represent a new beginning?

In the two and a half years since the initial publication of a Zeneca patent application revealing anilinoquinazolines as potent inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase (TK), several papers and patents have appeared describing TK inhibitors based on aminopyrimidine moieties. Such inhibitors appear to be greatly superior in potency and selectivity to the previous generation of TK inhibitors and have led to agents which appear to work selectively through the proposed mechanism. This article will start with an update on progress in the determination of relevant structures and mechanisms in kinases. A survey of the current literature on TK inhibitors of the pyrimidine family, updating and partially overlapping the review of Spada and Myers in a recent issue of this journal follows. The overview will finish by considering whether the current generation of inhibitors have the potential to answer some of the therapeutic questions raised by signal transduction approaches to cance...