An Informer Set of 481 small molecules was measured against 860 publicly available human CCLs encompassing 25 lineages. Small-molecule and cell-line information, including CCL contexts and growth conditions, is provided in Supplementary Data Sets 1–2 and the CTRP website (www.broadinstitute.org/ctrp ) and downloadable from the NCI-CTD2 Data Portal (ctd2.nci.nih.gov/). To verify that CCLs tested in sensitivity profiling uniquely matched those used to generate microarray expression measurements, genomic DNA was extracted from 803/860 CCLs tested (93%) and used to genotype 96 SNPs using the Fluidigm 96.96 system; SNP calls were matched to a database of 1045 CCLs7 (link),47 (link). 771 CCLs positively matched to a CCLE reference genotype; 32 (4%) did not match any reference CCL (Supplementary Data Set 1 ). As further information becomes available (e.g., matching of unconfirmed samples), we will provide updated information and analyses reflecting any changes at the NCI-CTD2 Data Portal and in the CTRP.
Small molecules were selected individually to interrogate important targets and/or cellular processes in cancer with high reported selectivity, and collectively to target diverse nodes in cancer cell circuitry, from sources including FDA-approved drugs, clinical candidates, previous screening and sensitivity profiling experiments, scientific literature and patents, bioactives, and collaborator contributions (Supplementary Data Set 2 )8 (link),12 (link). CCLs were plated at a density of 500 cells/well in white opaque tissue-culture-treated Aurora 1536-well MaKO plates (Brooks Automation) in the provider-recommended growth media using a highly automated platform. Compounds were added by acoustic transfer using a Labcyte Echo 555 (Labcyte Inc.) 24 hours after plating. The effects of small molecules were measured over a 16-point concentration range (two-fold dilution) in duplicate. DMSO was used at a constant concentration of 0.33%, including vehicle-only control wells. As a surrogate for viability, cellular ATP levels were assessed 72 hours after compound transfer by addition of CellTiterGlo (Promega) followed by luminescence measurement using a ViewLux Microplate Imager (PerkinElmer). Duplicates were averaged and luminescence values normalized to vehicle (DMSO) treatment and background (media-only) wells.
Small molecules were selected individually to interrogate important targets and/or cellular processes in cancer with high reported selectivity, and collectively to target diverse nodes in cancer cell circuitry, from sources including FDA-approved drugs, clinical candidates, previous screening and sensitivity profiling experiments, scientific literature and patents, bioactives, and collaborator contributions (