Drug–target residence time and its implications for lead optimization Academic Article uri icon

abstract

  • Much of drug discovery today is predicated on the concept of selective targeting of particular bioactive macromolecules by low-molecular-mass drugs. The binding of drugs to their macromolecular targets is therefore seen as paramount for pharmacological activity. In vitro assessment of drug-target interactions is classically quantified in terms of binding parameters such as IC(50) or K(d). This article presents an alternative perspective on drug optimization in terms of drug-target binary complex residence time, as quantified by the dissociative half-life of the drug-target binary complex. We describe the potential advantages of long residence time in terms of duration of pharmacological effect and target selectivity.

altmetric score

  • 22.66

author list (cited authors)

  • Copeland, R. A., Pompliano, D. L., & Meek, T. D.

citation count

  • 909

publication date

  • September 2006