Small-molecule inhibitors binding to protein kinases. Part I: exceptions from the traditional pharmacophore approach of type I inhibition

Abstract

Structural parameters of both inhibitors and kinases contribute to the complexity of designing kinase inhibitors. The continued study of high-resolution structures of ligand-enzyme complexes in combination with a more dynamic understanding of accessible conformational states of the target proteins, supported by detailed kinetic studies, will in the long-term help in developing new low-molecular weight kinase inhibitors.