Cellular Activity Should Require a Certain Affinity for the Target Enzyme

2 Cellular Activity Should Require a Certain Affinity for the Target Enzyme 

In an ideal situation a structural series of compounds will have unlimited cell permeability, and one can therefore expect a strict correlation between rank-order enzyme affinity (as measured by K, values) and the EC50 for cellular effects (the EC50 is the cellular or organismal equivalent of the in vitro IC50 i.e., the EC50 is the con- 

Often very subtle structural changes in a compound can cause significant changes in target enzyme affinity. Sometimes addition of a single methylene group 

0 z Good Enzyme Potency Good Cell Activity aX Poor Enzyme Potency Good Cell Activity 

3 Buildup of Substrate and/or Diminution of Product for the Target Enzyme Should Be Observed in Cells 

---