Abstract Designing a focused compound screening library of bioactive small molecules is a challenging task since many compounds modulate their effects through multiple protein targets with various degrees of potency and selectivity. We describe here several analytic procedures with adjustable cut-off parameters that enable one to design anticancer target-focused compound libraries optimized for library size, cellular activity, biological and chemical diversity and target selectivity. Even though our focus was on designing compound libraries to enable a comprehensive investigation of the target biology of glioblastoma (GBM), the compound collections cover a wide range of protein targets and biological pathways implicated in various types of cancers, making the libraries widely applicable in precision oncology studies. We published the final screening set library, called the C omprehensive anti- C ancer small- C ompound L ibrary, or C 3 L. We hope these general library design principles and the current, widely annotated small molecule libraries will prove useful for the community in various phenotypic screening experiments in GBM and other cancers.

Optimized chemogenomic library design strategies for precision oncology