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