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ChemBank (http://chembank.broad.harvard.edu/) is a public, web-based informatics environment developed through a collaboration between the Chemical Biology Program and Platform at the Broad Institute of Harvard and MIT. This knowledge environment includes freely available data derived from small molecules and small-molecule screens and resources for(More)
The high rate of clinical response to protein-kinase-targeting drugs matched to cancer patients with specific genomic alterations has prompted efforts to use cancer cell line (CCL) profiling to identify additional biomarkers of small-molecule sensitivities. We have quantitatively measured the sensitivity of 242 genomically characterized CCLs to an Informer(More)
High-throughput screening has become a mainstay of small-molecule probe and early drug discovery. The question of how to build and evolve efficient screening collections systematically for cell-based and biochemical screening is still unresolved. It is often assumed that chemical structure diversity leads to diverse biological performance of a library.(More)
The reduction of plasma low-density lipoprotein levels by HMG-CoA reductase inhibitors, or statins, has had a revolutionary impact in medicine, but muscle-related side effects remain a dose-limiting toxicity in many patients. We describe a chemical epistasis approach that can be useful in refining the mechanism of statin muscle toxicity, as well as in(More)
Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the(More)
Pancreatic beta-cell apoptosis is a critical event during the development of type-1 diabetes. The identification of small molecules capable of preventing cytokine-induced apoptosis could lead to avenues for therapeutic intervention. We developed a set of phenotypic cell-based assays designed to identify such small-molecule suppressors. Rat INS-1E cells were(More)
Most methods of deciding which hits from a screen to send for confirmatory testing assume that all confirmed actives are equally valuable and aim only to maximize the number of confirmed hits. In contrast, "utility-aware" methods are informed by models of screeners' preferences and can increase the rate at which the useful information is discovered.(More)
MOTIVATION In high-throughput screens (HTS) of small molecules for activity in an in vitro assay, it is common to search for active scaffolds, with at least one example successfully confirmed as an active. The number of active scaffolds better reflects the success of the screen than the number of active molecules. Many existing algorithms for deciding which(More)
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