Hypothesis-driven screening

Fig. 1. Process-driven versus hypothesis-driven screening.

Fig. 2. Hypothesis-driven screening combines iterative and parallel elements. H2L Hit-to-Lead.

In this section, we exemplify the power of hypothesis-driven screening. Three chemogenomics projects, and the impact of flexible experimental design enabled by HTCP Picking capabilities are discussed. Two of these examples are drawn from the area of infectious diseases the third example describes a neuroscience project. 

The in vitro screening approach measures direct mechanistic links between chemical interactions with key targets and the downstream effects of perturbing the related molecular pathways. By using current knowledge ofthe molecular basis of diseases, one can enrich an assay set to probe targets in key disease-related pathways and thereby develop predictive models in a more hypothesis-driven manner. 

Hypothesis-driven investigation FoUow up to TSA assessment of possible on-target risks and develop customized counter-screens Follow up to observed toxicities during in vivo studies to determine drivers (on-target versus off-target) and characterize translation risk and monitoring... 

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