In-house pharmaceutical collections are no longer sufficient for sampling chemical spaces. As novel bioactive chemotypes are successfully identified by virtual and high -throughput screening, the ability to rapidly sift through large numbers of chemicals prior to acquisition or experiment is required. Strategies for compound selection include some of the following steps: 1.) database assembly (in silico inventory); 2a.) structural integrity verification (keep unique structures only); 2b.) limited exploration of alternative chemical representations for the uniques (stereoisomers, tautomers, ionization states); 3.) property and structural filtering (remove unwanted structures); 4.) 3D-structure generation (for virtual screening or 3D-based similarity); 5a.) clustering or statistical design for selection; 5b.) similarity-based selection (if bioactives are known); 5c.) receptor-based selection (if target binding site is known); 6.) add a random subset to the final list.
Keywords: cheminformatics, drug discovery, high-throughput screening, leadlikeness, property filtering, unwanted structures, virtual screening
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