Diapositive 1

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)