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. 2014 Sep 22;54(9):2536-43.
doi: 10.1021/ci500092j. Epub 2014 Aug 29.

Curation and analysis of multitargeting agents for polypharmacological modeling

A Srinivas Reddy  1 , Zhi Tan, Shuxing Zhang
Affiliations

Curation and analysis of multitargeting agents for polypharmacological modeling

A Srinivas Reddy et al. J Chem Inf Model. .

Abstract

In drug discovery and development, the conventional "single drug, single target" concept has been shifted to "single drug, multiple targets"--a concept coined as polypharmacology. For studies in this emerging field, dedicated and high-quality databases of multitargeting ligands would be exceedingly beneficial. To this end, we conducted a comprehensive analysis of the structural and chemical/biological profiles of polypharmacological agents and present a Web-based database (Polypharma). All of these compounds curated herein have been cocrystallized with more than one unique protein with intensive reports of their multitargeting activities. The present study provides more insight of drug multitargeting and is particularly useful for polypharmacology modeling. This specialized curation has been made publically available at http:/imdlab.org/polypharma/

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Figures

Figure 1
Figure 1
Scheme of Polypharma database curation.
Figure 2
Figure 2
Comparison of SLogP, TPSA, and molecular weight in multiple-targeting ligands (the upper panel) vs single-targeting ligands (the lower panel). The plots represent the distribution density of the ligands in the 2D space in terms of the respective chemical/physical properties. The color represents the density as demonstrated by the bar. The color code and scale is the same in each comparison for multitargeting and single-targeting ligands.
Figure 3
Figure 3
Comparison of residue composition (the upper panel) and chemical/physical properties of protein binding pockets of multitargeting vs single targeting ligands.
Figure 4
Figure 4
Architecture implemented in the database.
Figure 5
Figure 5
Some of the screenshots of the graphical user interface of the Polypharma database.
See this image and copyright information in PMC

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