Abstract:
:Estimation of bioavailability and toxicity at the very beginning of the drug development process is one of the big challenges in drug discovery. Most of the processes involved in ADME are driven by rather unspecific interactions between drugs and biological macromolecules. Within the past decade, drug transport pumps such as P-glycoprotein (Pgp) have gained increasing interest in the early ADME profiling process. Due to the high structural diversity of ligands of Pgp, traditional QSAR methods were only successful within analogous series of compounds. We used an approach based on similarity calculations to predict Pgp-inhibitory activity of a series of propafenone analogues. This SIBAR approach is based on selection of a highly diverse reference compound set and calculation of similarity values to these reference compounds. The similarity values (denoted as SIBAR descriptors) are then used for PLS analysis. Our results show, that for a set of 131 propafenone type compounds, models with good predictivity were obtained both in cross validation procedures and with a 31-compound external test set. Thus, these new descriptors might be a versatile tool for generation of predictive ADME models.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Klein C,Kaiser D,Kopp S,Chiba P,Ecker GFdoi
10.1023/a:1023828527638subject
Has Abstractpub_date
2002-11-01 00:00:00pages
785-93issue
11eissn
0920-654Xissn
1573-4951journal_volume
16pub_type
杂志文章abstract::A three-dimensional quantitative spectrometric data-activity relationship (3D-QSDAR) modeling technique which uses NMR spectral and structural information that is combined in a 3D-connectivity matrix has been developed. A 3D-connectivity matrix was built by displaying all possible assigned carbon NMR chemical shifts, ...
journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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doi:10.1007/s10822-017-0061-2
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更新日期:2008-09-01 00:00:00
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journal_title:Journal of computer-aided molecular design
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doi:10.1007/s10822-019-00193-0
更新日期:2019-04-01 00:00:00
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journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-016-9946-8
更新日期:2016-09-01 00:00:00
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journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/BF00126748
更新日期:1994-06-01 00:00:00
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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journal_title:Journal of computer-aided molecular design
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