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.
You_Yue_BIBM2014_time_scale_analysis_of_receptor_enzyme_activity.pdf - Accepted Author Manuscript
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.
|Item type:||Conference or Workshop Item (Paper)|
|Notes:||© 2014 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.|
|Keywords:||receptor enzyme activity, drug discovery, time dependant dose response, Bioengineering, Electrical engineering. Electronics Nuclear engineering, Biomedical Engineering|
|Subjects:||Technology > Engineering (General). Civil engineering (General) > Bioengineering
Technology > Electrical engineering. Electronics Nuclear engineering
|Department:||Faculty of Engineering > Electronic and Electrical Engineering|
|Depositing user:||Pure Administrator|
|Date Deposited:||10 Nov 2014 14:49|
|Last modified:||02 Apr 2017 07:36|