iuphar-db, grac and the iuphar/bps guide to pharmacology
DESCRIPTION
PreTRANSCRIPT
![Page 1: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/1.jpg)
www.guidetopharmacology.org
IUPHAR-DB, GRAC andthe IUPHAR/BPS Guide to PHARMACOLOGYAdam J. PawsonMonday 14th July 2014, WCP2014
![Page 2: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/2.jpg)
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.
![Page 3: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/3.jpg)
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
![Page 4: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/4.jpg)
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.
![Page 5: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/5.jpg)
The IUPHAR/BPSGuide to PHARMACOLOGY
• A single entry point to pharmacological information originally contained in IUPHAR-DB and the 5th (2012) Edition of GRAC;
![Page 6: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/6.jpg)
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’.
![Page 7: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/7.jpg)
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
![Page 8: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/8.jpg)
![Page 9: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/9.jpg)
Constructing the IUPHAR/BPSGuide to PHARMACOLOGY
![Page 10: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/10.jpg)
![Page 11: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/11.jpg)
Database content (Targets)
![Page 12: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/12.jpg)
Database content (Ligands)
![Page 13: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/13.jpg)
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.
![Page 14: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/14.jpg)
Target pages
![Page 15: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/15.jpg)
Target pages (2)
![Page 16: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/16.jpg)
Target pages (3)
![Page 17: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/17.jpg)
![Page 18: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/18.jpg)
![Page 19: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/19.jpg)
![Page 20: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/20.jpg)
Target pages 4
![Page 21: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/21.jpg)
Target pages 5
![Page 22: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/22.jpg)
Target pages 6
![Page 23: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/23.jpg)
Target pages 7
![Page 24: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/24.jpg)
Target pages 8
![Page 25: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/25.jpg)
Peptides
![Page 26: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/26.jpg)
Peptides
![Page 27: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/27.jpg)
Antibodies
![Page 28: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/28.jpg)
Antibodies
![Page 29: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/29.jpg)
Antibodies
![Page 30: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/30.jpg)
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.
![Page 31: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/31.jpg)
KinaseslestaurtinibImatinib
![Page 32: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/32.jpg)
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.
![Page 33: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/33.jpg)
Proteases and hydrolases
![Page 34: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/34.jpg)
Epigenetics• We provide annotation on 127
epigenetics targets (chromatin modifying enzymes and bromodomain-containing proteins), along with activity data for 41 inhibitors.
![Page 35: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/35.jpg)
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.
![Page 36: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/36.jpg)
![Page 37: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/37.jpg)
![Page 38: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/38.jpg)
![Page 39: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/39.jpg)
Live demos
• Booth # 70 • Booth # 87-89
![Page 40: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/40.jpg)
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
![Page 41: IUPHAR-DB, GRAC and the IUPHAR/BPS Guide to PHARMACOLOGY](https://reader031.vdocuments.net/reader031/viewer/2022012321/53fb47aa8d7f729c2e8b56cc/html5/thumbnails/41.jpg)