کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361228 981459 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Extraction of tacit knowledge from large ADME data sets via pairwise analysis
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Extraction of tacit knowledge from large ADME data sets via pairwise analysis
چکیده انگلیسی

Pharmaceutical companies routinely collect data across multiple projects for common ADME endpoints. Although at the time of collection the data is intended for use in decision making within a specific project, knowledge can be gained by data mining the entire cross-project data set for patterns of structure–activity relationships (SAR) that may be applied to any project. One such data mining method is pairwise analysis. This method has the advantage of being able to identify small structural changes that lead to significant changes in activity. In this paper, we describe the process for full pairwise analysis of our high-throughput ADME assays routinely used for compound discovery efforts at Pfizer (microsomal clearance, passive membrane permeability, P-gp efflux, and lipophilicity). We also describe multiple strategies for the application of these transforms in a prospective manner during compound design. Finally, a detailed analysis of the activity patterns in pairs of compounds that share the same molecular transformation reveals multiple types of transforms from an SAR perspective. These include bioisosteres, additives, multiplicatives, and a type we call switches as they act to either turn on or turn off an activity.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 12, 15 June 2011, Pages 3739–3749
نویسندگان
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