Investigating receptor enzyme activity using time-scale analysis

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You, Tao and Yue, Hong (2015) Investigating receptor enzyme activity using time-scale analysis. IET Systems Biology, 9 (6). pp. 268-276. ISSN 1751-8849 (https://doi.org/10.1049/iet-syb.2015.0037)

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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.

ORCID iDs

You, Tao and Yue, Hong ORCID logoORCID: https://orcid.org/0000-0003-2072-6223;
  • Item type:Article
    ID code:55252
    Dates:
    Date
    Event
    19 November 2015
    Published
    31 May 2015
    Accepted
    Notes:This paper is a postprint of a paper submitted to and accepted for publication in IET Systems Biology and is subject to Institution of Engineering and Technology Copyright. The copy of record is available at IET Digital Library
    Subjects:Technology
    Department:Faculty of Engineering > Electronic and Electrical Engineering
    Depositing user: Pure Administrator
    Date deposited:06 Jan 2016 12:03
    Last modified:11 Nov 2024 11:17
    URI:https://strathprints.strath.ac.uk/id/eprint/55252
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