2. Identifying consensus lists of approved drugs & targets
2. Curated information on approved drugs
Helen E. Benson1, Elena Faccenda1, Christopher Southan1, Joanna L. Sharman1, Adam J. Pawson1, Michael Spedding2, Anthony J. Harmar1, Jamie Davies1 and NC-IUPHAR*1The Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK. 2 Spedding Research Solutions SARL, 6 Rue Ampere, Le Vesinet, 78110,
France. * The International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification.
1. About the ‘Guide to PHARMACOLOGY’
What is the Guide to PHARMACOLOGY?The IUPHAR/BPS Guide to PHARMACOLOGY Web portal is an open access resource providing overviews of the key properties, background reading and selective ligands of a wide range of biological targets. For selected targets, overview pages link to more detailed information including data on biological variants, tissue distribution, signalling mechanisms and pathophysiological role. The portal also provides access to the International Union of Basic and Clinical Pharmacology (IUPHAR) database, and links to the Concise Guide to PHARMACOLOGY 2013/2014, a publication snapshot created from the database overview pages and published in the British Journal of Pharmacology.
Which drug target classes are covered?• G protein-coupled receptors (GPCRs) including orphan GPCRs and adhesion GPCRs• Voltage-gated ion channels (VGICs)• Ligand-gated ion channels (LGICs)• Other ion channels• Nuclear hormone receptors• Catalytic receptors• Transporters• Enzymes including peptidases and protein kinases • Other protein targets
www.guidetopharmacology.org
Approved drug and clinical target curation in the IUPHAR/BPS Guide to PHARMACOLOGY
We especially thank all contributors, collaborators and NC-IUPHAR members
Where do the data come from?All data are curated from the primary literature by an international network of >700 experts coordinated by the IUPHAR Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) and the Editors of the Concise Guide to PHARMACOLOGY.
Our ligand list now includes a list of all the approved drugs in the database. These compounds also appear in lists by molecular class e.g. synthetic organics, peptides, antibodies.
Recent developmentsThe Guide to PHARMACOLOGY is being expanded to include:
• All data-supported primary targets of prescription drugs • Targets of high research interest and clinical trial targets• Drug clinical use and mechanism of action• Quantitative data (typically IC50, Ki or Kd) supporting the link between
a drug and its primary target
Supported by:
4. Curation of information on approved drug targets
Search by disease name
Target pages include:
Interaction tables with approved drug and primary target annotation.
These tables can be ranked according to ligand name, species or affinity and are hyperlinked to ligand pages.
Clinically relevant mutations and pathophysiology table with links to OMIM disease pages and rare disease database Orphanet
It is now possible to search for targets and ligand by disease name.
Some endogenous peptide ligands are also targets of approved drugs, e.g. the cytokine targets of antibodies. These entities are curated with interlinked target and ligand pages.
To expand our coverage of clinical targets we have: • Intersected and analysed publically
available datasets to compile a consensus set of targets and approved drugs• Identified the molecular mechanisms of action of approved drugs• Developed stringent mapping criteria for curating primary targets of approved drugs • Established correct molecular structures for drug active components• Curated supporting quantitative data from literature
Primary target identification and mapping We arrived at a consensus list of targets of approved drugs (TOADS) by comparing published target lists from the following sources:ChEMBL 17; DrugBank; The Therapeutic Target Database (TTD); Rask-Anderson M. et al. Annu Rev Pharmacol Toxicol. 2014; 54:9-26.
Creating a list of approved drugs We compared sources (DrugBank, TTD, ChEMBL) within PubChem to identify a consensus list of approved drugs. Lists were merged and filtered to remove mixtures and low Mw structures. The results were then intersected with a Thompson Drugs of the Future list to identify additional drugs and with ~7000 INNs in PubChem to produce a 4-way corroborated list that will be expanded as the sources update.
ResultsWhile our activity mappings encompass some polypharmacology, we have chosen to annotate minimal rather than maximal target sets. Our small-molecule figures are currently converging to ~250 human protein primary targets for ~1000 consensus chemical structures of approved drugs. The resulting target and ligand lists are available to download from our website.
The clinical data tab includes a summary of the clinical use and the molecular mechanism of action. Curation of pharmacokinetic information for approved drugs is in progress.
Approved drug pages include curated chemical structures and calculated physico-chemical properties.
The summary tab for approved drugs now includes:
• Original FDA and/or EMA approval dates• IUPAC name• International Nonproprietary Name (INN) and
number • List of synonyms • Database links to other relevant resources
including DrugBank • Function to search PubMed for clinical trials,
titles and/or abstracts mentioning the drug.
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