The Affinity Advantage

Drug discovery is a complex, multi-parameter optimization process. I argue that a greater emphasis on optimizing binding affinity will accelerate the development of new medicines. Note that “optimizing” is not always synonymous with “maximizing.” Optimizing affinity provides seven distinct benefits: achieving potent tool compounds more quickly; making compounds with increased potency; making more selective compounds; optimizing drug candidates more quickly; encouraging the pursuit of more synthetically challenging compounds; expanding chemical diversity during lead optimization; and minimizing interactions with "avoid-ome” targets that lead to poor ADME and tox properties. While affinity is certainly not the only thing that matters, the value of optimizing drug – receptor interactions is profound and often underappreciated.