Investigating receptor enzyme activity using time-scale analysis

Tao You, Hong Yue

Research output: Contribution to journalArticle

1 Citation (Scopus)
59 Downloads (Pure)

Abstract

At early drug discovery, purified protein-based assays are often used to characterise compound potency. In the context of dose response, it is often perceived that a time-independent inhibitor is reversible and a time-dependent inhibitor is irreversible. The legitimacy of this argument is investigated using a simple kinetics model, where it is revealed by model-based analytical analysis and numerical studies that dose response of an irreversible inhibitor may appear time-independent under certain parametric conditions. Hence, the observation of time-independence cannot be used as sole evidence for identification of inhibitor reversibility. It has also been discussed how the synthesis and degradation of a target receptor affect drug inhibition in an in vitro cell-based assay setting. These processes may also influence dose response of an irreversible inhibitor in such a way that it appears time-independent under certain conditions. Furthermore, model-based steady-state analysis reveals the complexity nature of the drug-receptor process.
Original languageEnglish
Pages (from-to)268-276
Number of pages9
JournalIET Systems Biology
Volume9
Issue number6
DOIs
Publication statusPublished - 19 Nov 2015

Keywords

  • biochemistry
  • cellular biophysics
  • drugs
  • enzymes
  • molecular biophysics
  • reaction kinetics

Fingerprint Dive into the research topics of 'Investigating receptor enzyme activity using time-scale analysis'. Together they form a unique fingerprint.

Cite this