The importance of drug-target residence time.
The importance of kinetics in drug-target interactions, and particularly the residence time of a drug with its target, is increasingly recognized to play a pivotal role in determining both the efficacy and toxicity of a drug. Drug residence time can often be demonstrated to be a key differentiating factor between drugs that act upon a common target. Drug-target residence time can result in either favorable or unfavorable outcomes, and the use of such information could lead to the more efficient design of best-in-class drugs. This review highlights several key concepts and observations related to drug-target residence time, and suggests the use of a kinetics-perceptive and energetics-informed approach to address the challenges facing current drug discovery efforts.
Zhang
Rumin
R
Schering-Plough Research Institute, New Lead Discovery, Kenilworth, NJ 07033, USA. rumin.zhang@spcorp.com
Monsma
Frederick
F
D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D055808:Drug Discovery / Q000379:methods*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D010599:Pharmacokinetics; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013997:Time Factors
D004364:Pharmaceutical Preparations