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IUPHAR/BPS Guide to Pharmacology

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Poster presented at the Elixir All-Hands Meeting in Lisbon, June 2019. Gives a broad summary of Guide to Pharmacology activities in the last year. Emphasising new tools and our extension into malaria pharmacology.

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IUPHAR/BPS Guide to Pharmacology

  1. 1. 3. Searching for targets and ligands 2. Current database content 8. References 1 Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK. 2 School of Life Sciences, University of Nottingham Medical School, Nottingham, UK. 3 Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge. 4 Spedding Research Solutions SAS, Le Vesinet, France. * The International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification. The IUPHAR/BPS Guide to PHARMACOLOGY 1. Introduction The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) is an open, expert-driven database of pharmacological targets and the substances that act on them [1]. It is a joint initiative between the British Pharmacological Society (BPS) and the International Union of Basic and Clinical Pharmacology (IUPHAR), which aims to cover the human targets of licensed drugs and other likely targets of future therapeutics. The information is presented at two levels: 1. Overviews of the key properties, selective ligands and further reading for a wide range of human biological targets, which forms the basis for the Concise Guide to PHARMACOLOGY (CGTP) [2]. 2. Detailed pharmacological, functional and clinical information for a subset of important targets. All data are curated from the primary literature by an international network of 500 experts in 96 subcommittees of the IUPHAR Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR). ~1,700 established or potential data-supported drug targets ~1,100 additional related proteins Across several target classes: GPCRs, NHRs, Enzymes, Ion-Channels, Catalytic Receptors, Transporter and other protein targets Various search tools are available to find targets and ligands by name, ID, reference, chemical structure similarity, or BLAST sequence search. A new Pharmacology Search Tool (Fig. 2) allows users to upload lists of protein IDs and find ligands that modulate them, from both the GtoPdb and ChEMBL [3] databases. 1. Harding SD, et al. (2018). Nucl. Acids Res. 46 (Issue D1): D1091-D1106. 2. Alexander SPH, et al. (2017). Br J Pharmacol. 174 (Suppl 1): S1-S446. 3. Bento AP, et al. (2014). Nucl. Acids Res. 42 (Database Issue): D1083-D1090. 4. Harding SD, et al. (2018). Nat Rev Immunol. Web Watch: https://doi.org/10.1038/s41577-018-0079-2 5. Medicines for Malaria Venture https://www.mmv.org/ In addition, for a “how-to” guide on using GtoPdb see: Sharman JL, et al. (2018) Curr Protoc Bioinformatics. 61: 1.34.1-1.34.46. 5. IUPHAR Guide to Immunopharmacology Launched in October 2018, the Wellcome Trust-funded IUPHAR Guide to Immunopharmacology (GtoImmuPdb; www.guidetoimmunopharmacology.org) extends the information stored about drug targets by associating them with processes, cell types and disease of relevance to immunology. Providing a knowledge base that, for the first time, connects immunology with pharmacology [4]. Christopher Southan1 , Simon D. Harding1 , Jane F. Armstrong1 , Elena Faccenda1 , Adam J. Pawson1 , Stephen P.H. Alexander2 , Anthony P. Davenport3 , Michael Spedding4 , Jamie A. Davies1 and NC-IUPHAR* 6. IUPHAR/MMV Guide to Malaria Pharmacology www.guidetopharmacology.org enquiries@guidetopharmacology.org @GuidetoPHARM 4. Comparing ligand affinity across species Ligand activity graphs provide a quick way to visualise affinity at different targets and across species. Box plots (Fig. 2A) summarise standardised activity data from GtoPdb and ChEMBL [3]. Individual data points, assay details and references are provided in an accompanying table (Fig. 2B). Figure 2. Chart and table showing palosuran activity at human and rat UT receptors. A B 7. Downloading data Data are available to download in various formats: • Lists of targets, ligands and interactions in CSV format • REST web services for computational access to data in JSON format • SQL database dump files • Interaction data are now available in RDF format for semantic integration ~9,400 ligands, over 7,000 with quantitative interaction data Includes experimental compounds, labelled ligands, antibodies, peptides, natural products and inorganic chemicals > 1,300 approved drugs, >800 with quantitative interaction data Figure 1. (A) Pharmacology Search Tool with searching restricted to 3 interactions per target. (B) Results show activity data summarised from GtoPdb and ChEMBL. Results from searches can be downloaded as a CSV file by clicking the Download button in the top right.  540 targets and over 1,000 ligands of relevance to immunopharmacology.  700 associations between ligands and disease  3,000 target to immuno process associations  300 target to cell type associations This expert curation seeks to bring the most valuable pharmacological data into the hands of immunology researchers, facilitating the crossover of their research into drug discovery and therapeutics A B We especially thank all contributors, collaborators and NC-IUPHAR members Since October 2017, collaboration between IUPHAR and Medicines for Malaria Venture (MMV) [5] to curate antimalarial compounds and Plasmodium molecular targets for approved drugs. To provide optimised access to GtoPdb data for the malaria research community. Key Features • Provides a unique access point to the antimalarial information in our expert-curated database • Designed in consultation with malaria researchers to provide tailored routes into browsing the antimalarial data • New customised views of the data have been developed that include parasite lifecycle stage and target species activity (shown below) Currently there are 57 antimalarial ligands curated in the database, covering 25 Plasmodium molecular targets. We submit all our curated antimalarial compounds, that include approved drugs, clinical candidates and research leads, to PubChem where they acquire GtoPdb-specific Substance Identifiers (SIDs). These currently merge into 57 Compound Identifiers (CIDs) that are fully searchable in PubChem.