Recent progress towards the identification of selective inhibitors of serine/threonine protein kinases.

ABSTRACT

Protein serine/threonine kinases figure prominently among the molecular targets currently being pursued by the pharmaceutical industry. Given the conserved tertiary structure and catalytic mechanism of the mammalian kinase superfamily, it is not surprising that the discovery of selective inhibitors has proven to be difficult. However, in the last two years, progress has accelerated and approaches that target the ATP binding site and antisense RNA have matured to the point of advancing compounds into clinical trials. The development of a structural basis for understanding the selectivity of the pyridinylimidazole class of p38 MAP kinase inhibitors has been a major advance in this area.