SummaryChemical probes are essential tools for understanding biological systems and for target validation, yet selecting probes for biomedical research is rarely based on objective assessment of all potential compounds. Here, we describe the Probe Miner: Chemical Probes Objective Assessment resource, capitalizing on the plethora of public medicinal chemistry data to empower quantitative, objective, data-driven evaluation of chemical probes. We assess >1.8 million compounds for their suitability as chemical tools against 2,220 human targets and dissect the biases and limitations encountered. Probe Miner represents a valuable resource to aid the identification of potential chemical probes, particularly when used alongside expert curation.

Background/Aims: Pharmacogenomics aims to rationalize drug use by minimizing drug toxicity and/or by increasing drug efficacy. A large number of genomic markers have been correlated with variable drug responses and severity of adverse drug reactions. Although a number of these drugs bear pharmacogenomic information in their labels - approved by regulatory agencies - and comprehensive drug/gene lists exist online, information related to the respective pharmacogenomic biomarkers is currently missing from such lists. Methods: We extracted information from the published literature and online resources and developed DruGeVar (http://drugevar.genomicmedicinealliance.org), an online resource triangulating drugs with genes and pharmacogenomic biomarkers in an effort to build a comprehensive database that could serve clinical pharmacogenomics. Results and Conclusions: A user-friendly data querying and visualization interface allows users to formulate simple and complex queries. Such a database would be readily applicable as a stand-alone resource or a plug-in module for other databases.

FINDbase (http://www.findbase.org) is a comprehensive data repository that records the prevalence of clinically relevant genomic variants in various populations worldwide, such as pathogenic variants leading mostly to monogenic disorders and pharmacogenomics biomarkers. The database also records the incidence of rare genetic diseases in various populations, all in well-distinct data modules. Here, we report extensive data content updates in all data modules, with direct implications to clinical pharmacogenomics. Also, we report significant new developments in FINDbase, namely (i) the release of a new version of the ETHNOS software that catalyzes development curation of national/ethnic genetic databases, (ii) the migration of all FINDbase data content into 90 distinct national/ethnic mutation databases, all built around Microsoft's PivotViewer (http://www.getpivot.com) software (iii) new data visualization tools and (iv) the interrelation of FINDbase with DruGeVar database with direct implications in clinical pharmacogenomics. The abovementioned updates further enhance the impact of FINDbase, as a key resource for Genomic Medicine applications.

Chemical probes are essential tools for understanding biological systems and for target validation, yet selecting tools for biomedical research is largely biased and subjective. Here we describe the Probe Miner: Chemical Probes Objective Assessment resource – capitalising on the plethora of public medicinal chemistry data to empower quantitative, objective, Big Data-driven assessment of chemical probes. We assess >1.8m compounds for their suitability as chemical tools against 2,220 human targets and dissect their biases and limitations.

canSAR (http://cansar.icr.ac.uk) is a freely available, multidisciplinary, cancer-focused knowledgebase developed to bring together information from genomic, transcriptomic, protein, pathway, chemical, pharmacologic, and 3D structural data. canSAR provides a powerful, uniqu,e and user-friendly portal to enable translational research and to help generate and test hypotheses and support scientific decision-making in drug discovery both before and after target selection. With its three alternative approaches to examine druggability, canSAR represents the most comprehensive public druggability assessment resource. canSAR provides 3D-structure-based druggability assessment for more than 3,100,000 cavities on more than 391,000 protein chains; ligand-based druggability assessment for 8,197 human proteins; and, more recently, protein network-based druggability results for 13,345 human proteins. Together these provide a powerful enabler for target selection and validation for drug discovery. Druggability assessments are presented alongside data from resources including 224,000 clinical trials from ClinicalTrials.gov, drug indications from Cancer.gov, target gene expression from TCGA for cell lines, and patient samples to provide a detailed picture of the target’s biologic context. Recent updates to canSAR include integration of ChEMBL 23 and additional curation of a protein-protein interaction network of 13,500 nodes. canSAR is currently used by more than 65,000 users annually from both academia and industry, and we will illustrate how canSAR can empower decision making in translational drug discovery. Citation Format: Elizabeth A. Coker, Patrizio Di Micco, Joesph E. Tym, Costas Mitsopoulos, Angeliki Komianou, Albert A. Antolin, Bissan Al-Lazikani. canSAR, a cancer research and drug discovery knowledgebase [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B096.