IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY

www.guidetopharmacology.org

IUPHAR-DB, GRAC andthe IUPHAR/BPS Guide to PHARMACOLOGYAdam J. PawsonMonday 14th July 2014, WCP2014

The history of IUPHAR-DB• The IUPHAR database of receptors and

channels has been under development since 2000;

• Developed by a team of curators, guided by NC-IUPHAR and its international network of expert contributors;

• In-depth coverage of the properties and pharmacology of G protein-coupled receptors, voltage- and ligand-gated ion channels, and nuclear hormone receptors.

The history of IUPHAR-DB (2)

– Peer-reviewed by NC-IUPHAR subcommittees; data include:• Gene and protein information• IUPHAR nomenclature and synonyms • Agonist , antagonist and allosteric modulator affinities• Transduction mechanisms; Tissue distribution• Functional assays; Physiological Functions• Mouse gene knockout phenotypes• Clinically-Relevant Mutations and Pathophysiology• Gene expression changes in pathophysiology; Biologically

significant variants– Extensively referenced and linked to primary literature in PubMed– Extensively linked to corresponding entries in other resources– Provides unambiguous ligand structural information and peptide

sequences

A new initiative• In early 2011 a collaboration was initiated

between IUPHAR and the British Pharmacological Society;

• To develop a single entry point to pharmacological information on drug targets and their ligands.

The IUPHAR/BPSGuide to PHARMACOLOGY

• A single entry point to pharmacological information originally contained in IUPHAR-DB and the 5th (2012) Edition of GRAC;

Introducing GRAC• The Guide to Receptors and Channels (GRAC);• Published since 2004; biennially by the British

Journal of Pharmacology;• Authoritative, but user-friendly publication,

which allows a rapid overview of the key properties of a wide range of established or potential pharmacological targets;

• Provides information succinctly, so that a newcomer to a particular target group can identify the main elements ‘at a glance’.

Introducing GRAC (2)– Concise target family summaries of the

key properties of over 2000 established or potential drug targets• G protein-coupled receptors• Ligand-gated ion channels• Other ion channels• Nuclear hormone receptors• Catalytic receptors• Enzymes• Transporters

– Overview summaries and comments on data

– Selective ligands and probes (radioligands and PET ligands where available)

– Further reading lists

Constructing the IUPHAR/BPSGuide to PHARMACOLOGY

Database content (Targets)

Database content (Ligands)

The IUPHAR/BPSGuide to PHARMACOLOGY

• A single entry point to pharmacological information originally contained in IUPHAR-DB and the 5th (2012) Edition of GRAC;

• Information presented in two levels of detail; concise and detailed views;

• Customised tables for selected targets.

Target pages

Target pages (2)

Target pages (3)

Target pages 4

Target pages 5

Target pages 6

Target pages 7

Target pages 8

Peptides

Peptides

Antibodies

Antibodies

Antibodies

Kinases• All the human protein kinases and selected lipid

kinases, including genomic and structural information for all the kinases;

• Additional information is provided on the 20 clinically-used kinase inhibitors [including summaries of clinical use and absorption, distribution, metabolism, and excretion (ADME) data];

• Selected bioactivity data for approved kinase inhibitors;

• Data from published screening assays by DiscoveRx, EMD Millipore and Reaction Biology are also included for 71, 158 and 176 kinase inhibitors respectively;

• DiscoveRx data include links to their TREEspot™ compound profile visualisation tool.

KinaseslestaurtinibImatinib

Proteases and hydrolases• The database includes pages with genomic

and structural information for 175 proteases and 14 hydrolases with activity records in ChEMBL;

• Detailed ligand activity (Ki or IC50) mapping has been curated for 46 proteases and 14 hydrolases for either approved prodrugs, drugs, clinical candidates or selected research compounds;

• MEROPS classification system adopted.

Proteases and hydrolases

Epigenetics• We provide annotation on 127

epigenetics targets (chromatin modifying enzymes and bromodomain-containing proteins), along with activity data for 41 inhibitors.

Drugs and Targets inAlzheimer’s disease

• Database search functionality enables retrieval of implicated ligands and targets by disease name;• A search for “Alzheimer’s

disease” returns database entries for 43 ligands and 13 targets.

Live demos

• Booth # 70 • Booth # 87-89

Acknowledgements• Tony Harmar• Michael Spedding, Steve Alexander, Ian

McGrath and members of NC-IUPHAR• NC-IUPHAR subcommittee chairs and

members• GRAC/Concise Guide contributors• Joanna Sharman, Helen Benson, Elena

Faccenda, Christopher Southan and Jamie Davies

• All past database curators