Small Molecule Inhibitors of the Class 1 Receptor Tyrosine Kinase Family

G.   Stuart   Cockerill; Karen   E.   Lackey

Abstract

This review covers literature describing research progress in erbB family tyrosine kinase inhibition over the last year. Excellent recent reviews are available, thus we have focussed on current developments of leading small molecule drug candidates as well as their erbB family inhibition profile. The most advanced erbB family tyrosine kinase (TK) inhibitors are demonstrating promising anti-cancer activity in clinical trials and are discussed. Several inhibition strategies are emerging: EGFR TK selective, irreversible TK inhibition and dual EGFR / erbB2 TK inhibitors. While small structural differences are seen in the leading compounds, the variations in their inhibition profiles and compound properties suggest that biological systems judge structural diversity differently. The readers attention is drawn to common issues of selectivity and potency generally encountered with kinase inhibitors.

Keywords: tyrosine kinase, anti-cancer activity, kinase inhibitors, malignant invasion of normal tissues, egfr tk, map kinase inhibitors, pyridinylimidazole, central nervous system disorders, imidazole ring, indole based inhibitors