Experimental Methods to Determine Binding Kinetics

Drugs interact with proteins and that interaction leads to the pharmacological response. It is recognized that biology is not at equilibrium and for some situations binding kinetics (kon and koff) may be a better predictor of a pharmacological response than the equilibrium constant. This chapter provides an overview of methods to measure the kinetics of small molecules binding to proteins. In general, binding kinetics can be determined using any analytical technique that allows measuring a change in concentration of an analyte with time. Accurate determination of binding kinetics can provide better estimate of pharmacokinetics/pharmacodynamics (PK/PD) relationships to assist clinical development. An increased ability to effectively measure binding kinetics and build structure kinetic relationships (SKR) leads to greater understanding of how to optimize binding kinetics toward clinical candidates with greater therapeutic indexes and therapeutic utility.