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Review
. 2018 Sep 29;7(4):29.
doi: 10.3390/ht7040029.

Current High-Throughput Approaches of Screening Modulatory Effects of Xenobiotics on Cytochrome P450 (CYP) Enzymes

Yee Tze Ung  1 , Chin Eng Ong  2 , Yan Pan  3
Affiliations
Review

Current High-Throughput Approaches of Screening Modulatory Effects of Xenobiotics on Cytochrome P450 (CYP) Enzymes

Yee Tze Ung et al. High Throughput. .

Abstract

Cytochrome P450 (CYP) is a critical drug-metabolizing enzyme superfamily. Modulation of CYP enzyme activities has the potential to cause drug⁻drug/herb interactions. Drug⁻drug/herb interactions can lead to serious adverse drug reactions (ADRs) or drug failures. Therefore, there is a need to examine the modulatory effects of new drug entities or herbal preparations on a wide range of CYP isoforms. The classic method of quantifying CYP enzyme activities is based on high-performance liquid chromatography (HPLC), which is time- and reagent-consuming. In the past two decades, high-throughput screening methods including fluorescence-based, luminescence-based, and mass-spectrometry-based assays have been developed and widely applied to estimate CYP enzyme activities. In general, these methods are faster and use lower volume of reagents than HPLC. However, each high-throughput method has its own limitations. Investigators may make a selection of these methods based on the available equipment in the laboratory, budget, and enzyme sources supplied. Furthermore, the current high-throughput systems should look into developing a reliable automation mechanism to accomplish ultra-high-throughput screening in the near future.

Keywords: cytochrome P450; high-throughput screening; in vitro; inhibitory effects.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Work flow of fluorescence-based assay.
Figure 2
Figure 2
Schematic of the metabolism of the ‘blocked’ dye substrate into a fluorescent metabolite.
Figure 3
Figure 3
Work flow of luminescence-based assay.
Figure 4
Figure 4
Work flow of mass spectrometry (MS)-based assay.
See this image and copyright information in PMC

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