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Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Application of Cytochrome P450 Drug Interaction Screening in Drug Discovery

Author(s): Robert S. Foti, Larry C. Wienkers and Jan L. Wahlstrom

Volume 13, Issue 2, 2010

Page: [145 - 158] Pages: 14

DOI: 10.2174/138620710790596718

Price: $65


Advances in drug interaction screening have resulted in reduced compound attrition rates due to unfavorable CYP-mediated drug interactions in clinical trials and improved patient safety. A major driver for the success in predicting drug interactions is a better understanding of the biological, chemical or mechanical factors that can impact the prediction of drug interactions in vitro. The enzyme source, probe substrate, accessory proteins and pharmacogenetics can all have profound effects upon the robustness and relevance of data generated with in vitro drug-drug interaction assays. Furthermore, the use of in silico techniques can potentially afford a priori knowledge of drug interaction potential, thus reducing the time and cost associated with drug interaction screening. This review will focus on recent advances in in vitro, in silico and bioanalytical techniques and demonstrate how these tools are currently used to provide effective CYP drug interaction screening in a discovery setting.

Keywords: P450, drug interactions, enzyme inhibition, in silico

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