Drug-target residence time and its implications for lead optimization. Academic Article

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.

authors

• Meek, Thomas

published proceedings

• Nat Rev Drug Discov

altmetric score

• 22.66

author list (cited authors)

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

citation count

• 1103

complete list of authors

• Copeland, Robert A||Pompliano, David L||Meek, Thomas D

publication date

• January 2006

publisher

• Springer Nature  Publisher

published in

• Nature Reviews Drug Discovery  Journal

keywords

• Binding, Competitive
• Drug Delivery Systems
• Drug Design
• Humans
• Kinetics
• Ligands
• Macromolecular Substances
• Pharmaceutical Preparations
• Technology, Pharmaceutical

Digital Object Identifier (DOI)

• 10.1038/nrd2082

start page

• 730

end page

• 739

volume

• 5

issue

• 9

URL

• http://dx.doi.org/10.1038/nrd2082