Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Cytochrome P450 networks in chemical space

Cytochrome P450 networks in chemical space A global analysis of the chemical space of cytochrome P450 enzymes in humans has not been achieved despite its great importance for drug metabolism and drug-drug interactions. We analyzed the global characteristics of cytochrome P450s by building several networks at the family, subfamily, and gene levels from information on P450 substrates, inducers, and inhibitors. These networks provide insight into the relationship of cytochrome P450 isoforms on the metabolism of drugs, changes in drug activity, and the promiscuous properties of each cytochrome P450 enzyme. From the networks, we analyzed the centrality of nodes and measured the strength of correlations between two nodes by drawing promiscuity maps. In addition, heat maps were generated to cluster cytochrome P450s by their similarity within three chemical spaces (substrates, inducers, and inhibitors). We observed the intra-linking and interlinking connections between three chemical spaces, the relative correlations of a given cytochrome P450 isoform with other isoforms, and the similarity of the metabolizing ability and changing pattern by chemicals. These results provide a global view of the relationship and similarity of cytochrome P450s on various chemical spaces at various levels. The measures of the strength of connection between two cytochrome P450s and the heat-map information could be used to predict drug-drug interactions, perform phylogenetic analyses, and further understand cooperative properties of these enzymes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Pharmacal Research Springer Journals

Cytochrome P450 networks in chemical space

Lee, Soyoung; Kim, Dongsup
Archives of Pharmacal Research , Volume 33 (9) – Sep 1, 2010
Download PDF
14 pages

Loading next page...
 
/lp/springer-journals/cytochrome-p450-networks-in-chemical-space-Xb7aD7S1kY

References (21)

Publisher
Springer Journals
Copyright
Copyright © 2010 by The Pharmaceutical Society of Korea and Springer Netherlands
Subject
Pharmacy; Pharmacology/Toxicology ; Pharmacy
ISSN
0253-6269
eISSN
1976-3786
DOI
10.1007/s12272-010-0910-1
pmid
20945135
Publisher site
See Article on Publisher Site

Abstract

A global analysis of the chemical space of cytochrome P450 enzymes in humans has not been achieved despite its great importance for drug metabolism and drug-drug interactions. We analyzed the global characteristics of cytochrome P450s by building several networks at the family, subfamily, and gene levels from information on P450 substrates, inducers, and inhibitors. These networks provide insight into the relationship of cytochrome P450 isoforms on the metabolism of drugs, changes in drug activity, and the promiscuous properties of each cytochrome P450 enzyme. From the networks, we analyzed the centrality of nodes and measured the strength of correlations between two nodes by drawing promiscuity maps. In addition, heat maps were generated to cluster cytochrome P450s by their similarity within three chemical spaces (substrates, inducers, and inhibitors). We observed the intra-linking and interlinking connections between three chemical spaces, the relative correlations of a given cytochrome P450 isoform with other isoforms, and the similarity of the metabolizing ability and changing pattern by chemicals. These results provide a global view of the relationship and similarity of cytochrome P450s on various chemical spaces at various levels. The measures of the strength of connection between two cytochrome P450s and the heat-map information could be used to predict drug-drug interactions, perform phylogenetic analyses, and further understand cooperative properties of these enzymes.

Journal

Archives of Pharmacal Research – Springer Journals

Published: Sep 1, 2010

There are no references for this article.