Klin Farmakol Farm. 2005;19(2):129-131

Ten years of efficient ATP site-directed competitive inhibition of proteinkinases

Jaroslav Veselý

Ústav patologické fyziologie, LF UP v Olomouci

A brief survey on the development of the first synthetic selective inibitors that competitively inhibit proteinkinases in their ATP-binding pocket is presented. Until 1990s, selective inhibition of this kind was considered improbable. The reason for such a belief was the high degree of homology existing between proteinkinase ATP-binding domains. The small synthetic molecules inhibiting c-Abl kinase, epidermal growth factor receptor kinase, and cyclin-dependent kinases (CDKs) were the first selective ATP-competitive inhibitors to have been described about ten years ago. French and Czech scientists made an important contribution in this field by discovering lead purine inhibitor olomoucine that competitively targets the CDK catalytic domain.

Keywords: Key words: proteinkinases, cyclin-dependent kinases, imatinib (Glivec), gefitinib (Iressa), olomoucine, roscovitine.

Published: January 1, 2006  Show citation