1. About the ‘Guide to PHARMACOLOGY’

3. Large scale kinase inhibitor profiling data

2. Curated information on enzymes

Elena Faccenda1, Christopher Southan1, Helen E. Benson1, Joanna L. Sharman1, Adam J. Pawson1,

Doriano Fabbro2, Jamie A Davies1, Michael Spedding3, and NC-IUPHAR*1The University of Edinburgh/Centre for Integrated Physiology, Edinburgh, EH8 9XD, UK; 2 Piqur Therapeutics, Hohe Winde Strasse 21, CH-4039 Riehen, Switzerland; 3 Spedding Research Solutions SARL, 6Rue Ampere, Le Vésinet 78110, France.* The International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification.

What is the Guide to PHARMACOLOGY?

The Guide to PHARMACOLOGY (GtoPdb) web portal is an open

access resource providing general overviews of the key propertiesof a wide range of biological targets, including selective ligandinformation and access to relevant publications. Our detailedtarget information is uniquely expert- and wholly manually-

curated. One aim of GtoPdb is to include all targets of approveddrugs and drugs in development, mapping interaction data forthe drugs to their primary molecular target(s). Recent GtoPdbexpansions have seen the introduction of target families forclinically important enzymes and associated biological and chemicalmodulators.

Which enzyme drug targets are included?• All proteins of the human kinome (>500)• Proteinases (>180)• Chromatin modifying enzymes (>90)• ‘Other’ enzymes such as DNA

topoisomerases and small monomeric GTPases

www.guidetopharmacology.org

Enzymes as drug targets: curated pharmacological information

in the ‘Guide to PHARMACOLOGY’enquiries@guidetopharmacology.org

Supported by:

We especially thank all contributors, collaborators and NC-IUPHAR members

Figure 1. Some enzyme database tables

What kinds of data are provided about drug targets?• Comprehensive information on nomenclature, structure,

genomics, physiological function, tissue distribution, functionalassays, biologically significant variants, pathophysiology,transduction mechanisms, ion conductance, heteromericcomplexes and more.

• Pharmacological information includes the affinities of selectedligands and drugs, including potent and selective agonists,antagonists, modulators and pore blockers, as well asradiolabelled ligands and monoclonal antibodies.

• Links are provided to important and useful resources such asPubMed, Uniprot, Entrez Gene, RefSeq, human, rat and mousegenome databases, the Protein Data Bank (PDB) and Wikipedia.

Where do the data come from?All data are curated from the primary literature by an internationalnetwork of >700 experts coordinated by the IUPHAR Committee onReceptor Nomenclature and Drug Classification (NC-IUPHAR) andthe Editors of The Concise Guide to PHARMACOLOGY.

What kind of information is provided?• Enzymes are organised into hierarchical groups within functional families and

subfamilies• Genomic information, official gene and protein nomenclature, and previous and

unofficial nomenclature.• Extensive links to external databases, including information on post-translational

modifications in PhosphoSitePlus®, substrates in the Human Protein ReferenceDatabase, and 3D structures in PDB and linked to enzyme reaction data in IUBMBand KEGG.

What kinds of data are included?• Affinity data and/or % inhibition data for

ligand profiling sets generated by DiscoveRX,EMD Millipore and Reaction Biology.

• Manually curated cellular data for approvedkinase inhibitors, including approvedmonoclonal antibodies.

Additional information:• Structural information for all of the ligands,

ligand synonyms, Approved drug status,International Nonproprietary Names (INNs),and links to external chemistry related

databases.• Direct access to DiscoveRx TREEspot™ Profile

images for inhibitor activity.• Molecular mechanism of action, clinical use

and ADME information for approved kinaseinhibitors.

Figure 2. Examples of screening datasets and inhibitor ligand

pages4. Plans for the future

• Regularly update the GtoPdb to include novel drug targets and innovative therapeutics, including expansion of approved indications and curators’ notes highlighting repurposing efforts.

• Include toxicity data, potentially expanding some of our current cytochrome p450 enzyme pages.

• Increase the coverage of introductory materials for important clinical targets.• Pilot sub-portals providing easily accessible pharmacological data targeted to specific

research communities (for example a stem-cell section, an environmental pharmacology section or an immunopharmacology section).