title: In silico prediction of cytochrome P450-mediated drug metabolism.
abstract: The application of combinatorial chemistry and high-throughput screening technique enables the large number of chemicals to be generated and tested simultaneously, which will facilitate the drug development and discovery. At the same time, it brings about a challenge of how to efficiently identify the potential drug candidates from thousands of compounds. A way used to deal with the challenge is to consider the drug pharmacokinetic properties, such as absorption, distribution, metabolism and excretion (ADME), in the early stage of drug development. Among ADME properties, metabolism is of importance due to the strong association with efficacy and safety of drug. The review will focus on in silico approaches for prediction of Cytochrome P450-mediated drug metabolism. We will describe these predictive methods from two aspects, structure-based and data-based. Moreover, the applications and limitations of various methods will be discussed. Finally, we provide further direction toward improving the predictive accuracy of these in silico methods.
authors.affiliation: Key Laboratory of Microbial Metabolism, Luc Montagnier Biomedical Research Institute , College of Life Science and Biotechnology, Shanghai Jiaotong University, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Limin Angela
authors.initials: LA
authors.lastname: Liu
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Wei
mesh_terms: D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D055808:Drug Discovery; D064420:Drug-Related Side Effects and Adverse Reactions; D057166:High-Throughput Screening Assays / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System