Figure 1.
Approach used to identify potent and selective (over α3β4) α4β2 ligands. Starting with just 34 samples comprised of >5 million compounds in the Scaffold Ranking Library, a specific Positional Scanning Library (1169) was identified for screening. This library contained 110 samples, and the results from screening the library were used in the selection of 18 compounds that were synthesized and tested (Deconvolution). On the basis of these results, eight new optimized compounds were synthesized and tested and found to be potent and selective (over α3β4) α4β2 ligands. In total, only 170 samples were tested; this shows the broad utility of this approach for many assay formats, especially those limited for whatever reason by throughput.