The free DNA exhibits base stacking features similar to those observed in X-ray structures

compounds that validated, or in several instances invalidated, newly proposed drug targets. Hit rates were consistently 25% to 80%, even for novel scaffolds completely unrelated to the known inhibitors. Biochim Biophys Acta. Author manuscript; available in PMC 2016 November 11. Martin et al. Page 5 2.3 Biochemical and cellular assay panels and computational target identification Author Manuscript Author Manuscript Author Manuscript Author Manuscript Panels of biochemical and cellular assays have been used in multiple ways to understand potential uses of kinase inhibitors to treat various cancers. The signatures together with Genetic backgrounds, mRNA expression levels and shRNA data have in turn been used to understand compound signatures, with the goal of creating patient tailoring hypotheses. Thibault Varin showed how one could utilize kinase inhibitor profiles to elucidate reasons for cell panel signature similarity. In several cases, a target hypothesis could be derived, indicating and confirming the role of PLK1 in cell proliferation. He presented comparisons of compounds based on the activity on large Piclidenoson cancer cell sensitivity and kinase affinity panels. By integrating these two compound profiles, he showed that the target toward which a compound has been historically optimized doesn’t necessarily drive the cellular activity of a given cell line or even of the overall cancer cell line panel. A RSK and a FAK inhibitor were reported to have a similar cancer cell sensitivity panel as a PLK1 inhibitor. These compounds both showed affinity for PLK1 in the kinase panels . Eric Martin applied Protein Family Virtual Screening to predict the IC50s for 3 million compounds against 2000 biochemical and cellular assays. These were applied to predicting polypharmacology, modes-of-action for phenotypic screens, toxicity profiling, and selecting commercial compounds with diverse selectivity profiles for chemical archive enhancement. Alexander Baumann described the extension of the well-established kinomescan methodology to the bromodomain family. Screening kinase inhibitor libraries against a bromodomain panel identified several established kinase inhibitors that were cross-reactive and might be repurposed as kinase-BRD dual inhibitors. He also PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1985776 introduced the”BioMAP” technology platform that provides a measure of overall phenotypic response of compounds under disease-like conditions, and identifies clinically relevant activities across a broad protein biomarker panel. The BioMAP systems are stimulated primary human cell types and co-cultures designed to recapitulate the complex signaling networks and microenvironment in diseased human tissue. The resulting biomarker fingerprints are useful for identifying modes of action and toxicity profiling. The biomarker fingerprints from the kinase/BRD dual inhibitors showed a hybrid of both mechanisms. Richard Engh examined methods to evaluate protein kinase target similarities with the aim to compare information types hierarchically. At the simplest level, “pseudosequence” similarities were calculated based on sequences chosen to represent binding site residues. Statistically, these corresponded quite well with experimental inhibition profiles from Ambit 2011 data, especially for tyrosine kinase targets. Such analyses support the use of surrogate kinases in structure-based drug discovery, and may aid in choosing focused screening libraries for repurposing or retargeting known compounds. At a higher level of