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. 2013 Jun 17;8(6):e62906.
doi: 10.1371/journal.pone.0062906. Print 2013.

The open access malaria box: a drug discovery catalyst for neglected diseases

Thomas Spangenberg  1 , Jeremy N Burrows, Paul Kowalczyk, Simon McDonald, Timothy N C Wells, Paul Willis
Affiliations

The open access malaria box: a drug discovery catalyst for neglected diseases

Thomas Spangenberg et al. PLoS One. .

Abstract

Historically, one of the key problems in neglected disease drug discovery has been identifying new and interesting chemotypes. Phenotypic screening of the malaria parasite, Plasmodium falciparum has yielded almost 30,000 submicromolar hits in recent years. To make this collection more accessible, a collection of 400 chemotypes has been assembled, termed the Malaria Box. Half of these compounds were selected based on their drug-like properties and the others as molecular probes. These can now be requested as a pharmacological test set by malaria biologists, but importantly by groups working on related parasites, as part of a program to make both data and compounds readily available. In this paper, the analysis and selection methodology and characteristics of the compounds are described.

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Conflict of interest statement

Competing Interests: PK is employed by SCYNEXIS, Inc. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Venn diagram presenting the overlap of structures in the St. Jude, Novartis and GSK datasets.
The data was generated using Pipeline Pilot 8.5, and displayed using R 2.14.1.
Figure 2
Figure 2. St Jude's, Novartis and GSK datasets profiled with respect to molecular weight, the number of hydrogen-bond donors, ALogP and N+O (nitrogen count plus oxygen count).
Figure 3
Figure 3. Principal Component Analysis plots.
Chemical diversity of the GSK, Novartis and St Jude libraries displayed (Panel A); Overlap in chemical diversity of the combined datasets and the commercially available compounds (Panel B); Overlap in chemical diversity of the commercially available compounds where the drug-like and probe-like chemotypes were annotated (Panel C).
Figure 4
Figure 4. Topological Polar Surface Area versus the ALogP for the Malaria Box drug-like set (green) and probe-like set (red).
Displayed with Vortex (v2012.11.17233) Dotmatics Limited 2007, 2012.
Figure 5
Figure 5. Molecular weight distribution for the drug-like set (blue) and probe-like set (green).
Displayed with Vortex (v2012.11.17233) Dotmatics Limited 2007, 2012.
Figure 6
Figure 6. Selection process for the Malaria Box.
Figure 7
Figure 7. Correlation (Log scale) between the P. falciparum 3D7 and K1 EC50s for the Malaria Box compounds resulting from the confirmatory screen.
Displayed with Vortex (v2012.11.17233) Dotmatics Limited 2007, 2012.
See this image and copyright information in PMC

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