| Prediction of cytochrome P450 2B6-substrate interactions using pharmacophore ensemble/support vector machine (PhE/SVM) approach. | |
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MedLine Citation:
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PMID: 18673154 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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An in silico model for predicting human cytochrome P450 2B6-substrate interactions was generated based on a novel scheme, which was initially devised to predict the hERG liability (reported in Leong, M. K., Chem. Res. Toxicol., 2007, 20, 217.) using pharmacophore ensemble/support vector machine to take into account the protein conformational flexibility while interacting with structurally diverse substrates. This is of critical importance yet never being addressed by any analogue-based molecular modeling studies before. Thirty-seven molecules were chosen from the literature and scrutinized for structural integrity and data consistency, of which 26 were treated as the training set to generate models, which were subject to validation by the other 11 molecules as the test set. The predicted pK(m) values by the final PhE/SVM model were in good agreement with observed values. In addition, this in silico model produced an r(2) of 0.84 and a 10-fold cross-validation q(2) of 0.66 for the training set and an r(2) of 0.87 for the test set, asserting the fact that this PhE/SVM model is an accurate model to predict the human P450 2B6-substrates interactions and can be used as a robust prediction tool to facilitate drug discovery. |
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Authors:
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Max K Leong; Tzu-Hsien Chen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Medicinal chemistry (Shāriqah (United Arab Emirates)) Volume: 4 ISSN: 1573-4064 ISO Abbreviation: - Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-08-04 Completed Date: 2008-09-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101240303 Medline TA: Med Chem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 396-406 Citation Subset: IM |
Affiliation:
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Department of Chemistry, National Dong Hwa University, Shoufeng, Hualien, Taiwan. leong@mail.ndhu.edu.tw |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cytochrome P-450 Enzyme System
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metabolism* Humans Models, Molecular Molecular Conformation Structure-Activity Relationship Substrate Specificity |
| Chemical | |
Reg. No./Substance:
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9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Cytochrome P-450 2B6, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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