Highlights • Existing small-molecule collections vary greatly on selectivity and target coverage • A data-driven approach to library design enhances diversity and library performance • The LSP-OptimalKinase library enhances selectivity and coverage for kinome targets • The LSP-MoA library optimally targets 1,852 genes in the liganded genome Summary Libraries of well-annotated small molecules have many uses in chemical genetics, drug discovery, and therapeutic repurposing.
