Krippendorff, Ben-Fillippo and Lienau, Philip and Reichel, Andreas and Huisinga, Wilhelm (2007) Optimizing Classification of Drug-Drug Interaction Potential for CYP450 Iso-Enzymes Inhibition Assays in Early Drug Discovery. Journal of Biomolecular Screening, 12 (1). pp. 92-99. ISSN 1087-0571

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Abstract

In drug discovery, the potential of cytochrome P450 inhibition of new chemical entities (NCEs) is frequently quantified in terms of IC50 values. In early drug discovery a risk-classification into low, medium or high potential inhibitors is often sufficient for ranking and prioritizing of compounds. While often six or more inhibitor concentrations are used to determine the IC50 value, the question arises whether it is possible to predict the risk-class based on fewer inhibitor concentrations with comparable reliability. In the present article we propose a new integrated twopoint method with inhibitor concentrations chosen in accordance with the risk-classification. We analyse its predictive power and the feasibility to not only classify the compounds into different risk classes but also rank those compounds that have been binned into the middle risk class. The proposed integrated two point method is thus highly suitable for automation. Altogether it maintains the quality of the prediction while considerably reducing time and cost. The proposed method is applicable to other IC50 assays and risk classifications.

Item Type:	Article
Keywords:	Drug-drug interaction; Cytochrome P450; Drug discovery; High throughput; IC50; Hamilton Institute.
Academic Unit:	Faculty of Science and Engineering > Research Institutes > Hamilton Institute
Item ID:	1750
Identification Number:	https://doi.org/10.1177/1087057106295897
Depositing User:	Hamilton Editor
Date Deposited:	15 Dec 2009 12:27
Journal or Publication Title:	Journal of Biomolecular Screening
Publisher:	Sage Publications
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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