Mechanisms of small molecule action (TK-inhibitors) I
Initial concerns: well conserved ATP-binding sites in between the
family of kinases: can we get specificity?
Using protein cristallography and NMR-spectroscopy sophisticated
structure-based design of specific kinase-inhibitors are now feasible
Kinase inhibitors were developed with the goal of highest selectivity,
however, several clinically approved kinases inhibitors are potent
inhibitors of multiple kinases: reason for potency?
Potential to target multiple distinct processes (hallmarks) associated
with tumor growth, but might be more toxic
Several preclinical studies demonstrate (supra-) additive effect by
combined treatment modalities mAB plus TK-inhibitors
(complementary effects)