Hit finding

In hit finding, a large number of compounds, the so-called library, is screened v. a target to identify components that bind. Libraries can meet different types of requirements, and efforts are made to optimize them with respect to diversity, solubility, drug-like character (see Table 1), and the synthetic accessibility of the compounds they contain. Substance libraries can contain small organic fragments, synthetic compounds of diverse chemical structures, or natural products.  

STD spectroscopy offers several advantages. First, there is almost no upper limit for the size of the target, even membrane proteins or immobilized targets are applicable.  

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Recently, structure-guided approaches have been used much more frequently at the hit-finding stage of drug discovery and, as this review seeks to demonstrate, these approaches have had a major impact on a number of kinase targets. The closer integration of these tools, combined with ongoing... 

Hit rates from HTS are often low and the hits obtained fail to progress into lead optimisation HTS is the predominant technique for hit finding employed by the majority of pharmaceutical companies and is central to modern drug discovery. However, many scientists are now regarding HTS as a costly necessity rather than a method of choice.191... 

Another important set of multiplexed assays monitor mRNA transcript levels. The expression level of all the genes involved in a known signal transduction pathway or other selective genes can be monitored simultaneously as a way of following compound effects on a cell. The current technologies for multiple mRNA detection include quantitative reverse transcriptional PCR (qRT-PCR), qNPA (quantitative nuclease protection assays), mass array assay technologies and branched DNA detection on Luminex beads (Panomics). The applications of such multiplexed in vitro and cell-based detection systems should provide more predicative information in hit finding and lead characterisation. 

NMR can assist the above process at different stages, namely, in hit finding, hit validation, and lead optimization. These three areas of application will be discussed in detail in the following sections. The drug discovery process is summarized in Figure 1, in which shaded boxes indicate where incorporation of NMR techniques is possible. 

In the following detailed discussion of the application of NMR techniques to drug discovery, a short description for hit finding, hit validation, and hit (lead) optimization is given. In addition, the corresponding requirements for the NMR experiments and the resulting implementations are described. Only typical experiments are given explicitly, but other techniques are sunamarized in Table 2. 

Im Silico Screening Hit Finding from Database Mining... 

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