Picture of neon light reading 'Open'

Discover open research at Strathprints as part of International Open Access Week!

23-29 October 2017 is International Open Access Week. The Strathprints institutional repository is a digital archive of Open Access research outputs, all produced by University of Strathclyde researchers.

Explore recent world leading Open Access research content this Open Access Week from across Strathclyde's many research active faculties: Engineering, Science, Humanities, Arts & Social Sciences and Strathclyde Business School.

Explore all Strathclyde Open Access research outputs...

Time scale analysis of receptor enzyme activity : irreversible inhibition sometimes exhibits incubation-time independence

You, Tao and Yue, Hong (2014) Time scale analysis of receptor enzyme activity : irreversible inhibition sometimes exhibits incubation-time independence. In: IEEE International Conference on Bioinformatics and Biomedicine (BIBM) 2014, 2014-11-02 - 2014-11-05, Hilton Hotel.

[img] PDF (You-Yue-BIBM2014-time-scale-analysis-of-receptor-enzyme-activity)
You_Yue_BIBM2014_time_scale_analysis_of_receptor_enzyme_activity.pdf - Accepted Author Manuscript

Download (562kB)


At early drug discovery, purified protein-based assays are often used to characterise compound potency. As far as dose response is concerned, it is often thought that a time-independent inhibitor is reversible and a time-dependent inhibitor is irreversible. Using a simple kinetics model, we investigate the legitimacy of this. Our model-based analytical analysis and numerical studies reveal that dose response of an irreversible inhibitor may appear time-independent under certain parametric conditions. Hence, time-independence cannot be used as evidence for inhibitor reversibility. Furthermore, we also analysed how the synthesis and degradation of a target receptor affect drug inhibition in an in vitro cell-based assay setting. Indeed, these processes may also influence dose response of an irreversible inhibitor in such a way that it appears time-independent under certain conditions. Hence, time-independent dose response in a cell assay also needs careful considerations. It is necessary to formulate a suitable model for analysis of protein-based assay and in vitro cell assay data to ensure a consistent understanding.