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. Author manuscript; available in PMC: 2011 Sep 30.
Published in final edited form as: Nat Rev Drug Discov. 2008 Oct 17;7(11):900–907. doi: 10.1038/nrd2684

Figure 1. Searching the TDR Targets database.

Figure 1

This figure shows the appearance of the search page and how different searches can be combined to yield lists of potential drug targets. First, the search can be restricted to a given species or groups of species; in this case Plasmodium falciparum is selected (top left panel). Next, one can query on function-based information. For example, selecting Enzyme under the Functional classific category of the Name/Annotation panel (top right) leads to a list of 862 genes identified in P. falciparum as encoding enzymes (bottom right). Similarly, the Structures panel below allows identification of the 4,829 genes for which there are crystal structures and/or high-quality structural models. Selecting within the “Phylogenetic distribution” panel (middle right) for orthologs present in Plasmodium vivax but not in humans or mice leads to 2,836 genes conserved in Plasmodium and absent in mammals. Very few genes have been validated as essential in P. falciparum, but an Essentiality search shows 1,162 P. falciparum genes with essential orthologs in at least one model organism – Caenorhabditis elegans, Escherichia coli, Mycobacterium tuberculosis, and Saccharomyces cerevisiae, and are therefore plausibly essential in P. falciparum. Each of these independent searches is stored in the History page of the database (bottom right). Registered users' queries are automatically saved for later sessions. The intersection of all four queries shown here have identified 25 potential drug targets for P. falciparum. These P. falciparum genes are potentially selective drug targets (they lack orthologous targets in mammals) that might allow for structure-based design of drugs (using available structures or models), are probably assayable (all are enzymes) and might be essential for viability (based on an ortholog being essential in some model organism). There are many promising drug targets in P. falciparum among this list (circled in red), supporting this approach as one means to prioritize promising targets.