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Drug Discov Today. 2018 Jan;23(1):12-16. doi: 10.1016/j.drudis.2017.07.016. Epub 2017 Aug 3.

Drug target residence time: a misleading concept.

Author information

1
Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden. Electronic address: rfolmer@yahoo.com.

Abstract

Since the importance of drug target residence time was first highlighted more 10 years ago, slow binding kinetics has received much attention in the drug discovery literature, and indeed within pharmaceutical research. However, the residence concept as presented in most papers is supported by rather misleading simulations and arguments, and by examples where compounds are taken out of their pharmacokinetic context. Moreover, fast association is typically more desirable than slow, and advantages of long residence time, notably a potential disconnect between pharmacodynamics (PD) and pharmacokinetics (PK), would be partially or completely offset by slow on-rate. Therefore, plain potency is likely a better predictor of drug development success than is residence time.

PMID:
28782685
DOI:
10.1016/j.drudis.2017.07.016
[Indexed for MEDLINE]

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