Target-Based Approaches

Within the malaria field, as mentioned, a few projects have delivered hits through target-based approaches (e.g., Pf (P. falciparum) DHODH). The DHODH project team, led by Prof. Margaret Phillips from the University of Texas South Western, ran a HTS of a compound collection against jy DHODH. They isolated several series of which one, a triazolopyrimidine, was selected for follow-up. This ultimately led to delivery of a preclinical candidate that, in 2014, delivered a positive proof of principle in a human challenge trial. This will be documented later as a specific case study. 

Target-based approaches are attractive because they allow the scientists to use the full range of tools at their disposal, for example, structural biology, while 

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A major approach to discovery is the target-based approach, whereby a single biological target is... 

Recombinant systems are the main tools of target-based approaches. These can be manipulated, but information is lacking for complete modeling of therapeutic systems. 

Spannhoff A., Heinke, R., Bauer, 1., Trojer, P., Meteger, E., Gust, R. etal. (2007) Target-based approach to inhibitors of histone arginine methyltransferases. Journal of Medicinal Chemistry, 50, 2319-2325. 

Once a target-based approach is embarked upon, the choice of target is the first step. In biological systems, there are generally four types of macromolecules that can interact with druglike molecules proteins, polysaccharides, lipids, and nucleic acids. As discussed in Chapter... 

With a target-based approach, the activity of molecules interacting with the previously identified target of interest can readily be assessed. As discussed previously, such an... 

It is clear that, measured by products in development or in the marketplace, target-based approaches to fungicide invention have not succeeded in delivering a rich... 

Genetic Approaches to generate Glufbsinate-Selectivity in Crops Target-based Approaches... 

If a focused approach is chosen, the success of the screen is directly linked to the most appropriate selection of compound libraries. Multiple strategies are available ranging from structure-based to target-based approaches. With the realization that the quality of the compounds is embedded in their structure or more precisely their physicochemical properties, property prediction and subsequent Altering play a crucial role in implementing quality into the screening set, which in turn will lead to attractive starting points. 

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