Database status report for GtoPdb from our April 2019 meeting in Paris

1. Database
progress reports

2. Overview
1. Database team activities
2. Web interface
3. Content expansion and updates
4. Concise Guide to PHARMACOLOGY (CGtP) 2019/20
5. Additional developmental and curatorial updates:
◦ IUPHAR Guide to IMMUNOPHARMACOLOGY (GtoImmuPdb)
◦ IUPHAR/MMV Guide to MALARIA PHARMACOLOGY (GtoMPdb)
 Please consult the accompanying April 2019 database report for
more in-depth detail
 We encourage discussion throughout this presentation – please
interrupt us

3. Database team
activities

4. Publications
◦ A new guide to immunopharmacology. Simon D. Harding, Elena Faccenda, Chris
Southan, Pasquale Maffia, Jamie A. Davies. Nature Reviews Immunology (Web
Watch). PMID: 30327546.
◦ SynPharm: A Guide to PHARMACOLOGY Database Tool for Designing Drug
Control into Engineered Proteins. Sam Ireland, Christopher Southan, Alazne
Dominguez, Simon Harding, Joanna Sharman, Jamie Davies. ACS Omega. Jul
31;3(7):7993-8002. PMID: 30087931
◦ Challenges of connecting chemistry to pharmacology: perspectives from
curating the IUPHAR/BPS Guide to PHARMACOLOGY. Christopher Southan,
Joanna L Sharman, Elena Faccenda, Adam J Pawson, Simon D Harding, Jamie A
Davies. ACS Omega. Jul 31;3(7):8408-8420. PMID:30087946
◦ Accessing expert-curated pharmacological data in the IUPHAR/BPS Guide to
PHARMACOLOGY. Joanna L Sharman, Elena Faccenda, Simon D Harding, Adam J
Pawson, Christopher Southan, Jamie A Davies and NC-IUPHAR (2018). Current
Protocols in Bioinformatics. 61: 1.34.1-1.34.46. PMID:30040201
◦ Caveat usor: assessing differences between major chemistry databases. Chris
Southan. ChemMedChem, 13(6):470-481. PMID 29451740

5. Public engagement
◦ Edinburgh Infectious Diseases 8th Annual Symposium, June 2019. Jane
Armstrong will present a poster on the Guide to MALARIA PHARMACOLOGY
◦ BioMalPar XV: Biology and Pathology of the Malaria Parasite, EMBL, Heidelberg,
May 2019. Jane Armstrong will present a poster on the Guide to MALARIA
PHARMACOLOGY
◦ BPS Pharmacology 2018, London, UK, Dec 2018. Simon Harding, Chris Southan,
Jamie Davies
◦ 5th European Congress of Immunology, Amsterdam, September 2018, Simon
Harding - presented poster on the Guide to IMMUNOPHARMACOLOGY
◦ 18th World Congress of Basic and Clinical Pharmacology, July 2018, Kyoto, Adam
Pawson and Chris Southan were in a Symposium on Computational
Pharmacology, Databases and Drug Discovery, and had two talks and several
posters
◦ ELIXIR All Hands 2018, Berlin, June 2018, Simon Harding
◦ Pharmacology Futures, Edinburgh, May 2018, Adam Pawson, Chris Southan,
Jamie Davies

6. Outreach and social media
FACEBOOK: The number of ‘likes’
increased to 4107 (March 2019), from
3749 in Sep 2018
TWITTER: @GuidetoPHARM has just
pipped 1,900 tweets, followers have
increased to 2670 from 2186 in Sep 2018
and our re-tweet rate has also gone up
LINKEDIN: The Curation Team have been
encouraging Subcommittee Chairs and
collaborators to increase their reciprocal
connectivity as individual LinkedIN users.
This expands our collective inter-network
outreach for posting updates, new
papers, etc.
BLOGGING: The Curation Team blog
(http://blog.guidetopharmacology.org/)
was receiving over ~670 views per month
over the last 6 months. This is our
primary news feed, includes database
release updates, new features, technical
items or articles
HOT TOPICS: As an established and
popular feature, our Hot Topics are
seeded in the form of new significant
pharmacology, drug discovery and key
human genomics papers. These are
communicated to us from NC-IUPHAR
and Subcommittee members, or picked
up from Twitter
SLIDESHARE: Our account
(http://www.slideshare.net/GuidetoPHAR
M) allows the database team to share
slide sets and posters with the
community thereby extending the reach
way beyond conference session direct
attendees. Our slide sets received 3,444
(+486) views over the past year

7. Interactions with database users
◦ We get a steady stream of user communications coming in to
enquiries@guidetopharmacology.org
◦ This is about one a week and they continue to cover a useful spectrum of
(mostly minor) fixes that we promptly address
◦ It is useful to catalogue these engagements as they provide valuable
information (not readily captured by analytics) in how and why GtoPdb is
used
◦ They also provide useful ideas for future development
◦ Some examples of the above are in the accompanying report
◦ Additionally, we also receive a steady stream of emails from BJP/BJCP
authors enquiring alerting us to missing links for ‘key’ ligands and targets for
possible inclusion in accepted articles
◦ In appropriate cases, we then add these entities and the new reference

8. Interactions with other resources
ELIXIR: Engagements continue with this important Europe-
wide bioinformatics infrastructure initiative. GtoPdb is a UK
Node Resource. https://elixiruknode.org/
PUBCHEM: We continue our important interactions with PubChem, including by both
mail and TC conversations with Evan Bolton, Paul Theissen and other members of the
team
IUPHAR PHARMACOLOGY EDUCATION PROJECT (PEP): The IUPHAR Pharmacology
Education project continues to be developed “as a learning resource to support
education and training in pharmacological sciences”. The PEP celebrated its 4th birthday
on 1st April 2019
JOURNAL < - > DATABASE CONNECTIVITY: The journal-to-GtoPdb linking initiative
PMID 25965085) for the BJP since Oct 2014 and BJCP since Nov 2016, can be counted
via the reference citations to our Concise Guide and NAR papers. The results indicate
outlinks for ~ 80% of BJP papers and ~ 50% for BJCP

9. Skye/Links Project
• Skye: ERC Consolidator Grant (James Cheney) to develop
programming language support for data curation. Dr. Simon
Fowler is the post-doc working on this.
• Links: Research programming language with support for multi-
tier web programming, language integration, and provenance
tracking
• Aims:
• Reimplement GtoPdb in Links
• Apply language features to a real-world scientific database
• Identify new language features useful for data curators
• Progress: Most core functionality implemented; hoping to start
on curation interface soon

10. Skye/Links Project
• http://homepages.inf.ed.ac.uk/jcheney/group/skye.html
• Re-implementation of GtoPdb is useful to stress-test Links. It is
the largest real-world application ever written in Links
• Real benefit could be implementation of archiving and
provenance tracking within the curation tool
• Feedback from Simon Fowler describes the database schema of
GtoPdb as ‘excellent’ and ‘very easy to understand and work
with’.

11. Interactions with suppliers
◦ In May 2018 we accepted sponsorship from Tocris
(https://www.tocris.com) in return for providing product supplier links
on our ligand summary pages
◦ This sponsorship was limited to one year. In total, we mapped 1258
GtoPdb ligand to Tocris compounds
◦ We have agreed to continue this arrangement and update these
sponsored links. We have begun preparations for the update and have
been provided with an updated set of compounds from Tocris. These
currently map to 1369 GtoPdb ligands. The new links will go live in
May 2019

12. Web interface

13. Database access statistics
Monthly
statistics
Apr 2018 - Mar 2019
(previous 12
months)
Sessions 33,671 (31,255)
Users 22,071 (20,293)
Page views 115,765 (16,939)
Pages / Session 3.44 (3.42)
Avg. Session
Duration
00:03:22 (00:03:18)

14. Acquisition, browsers and devices
◦ It is useful to be aware of where users are accessing GtoPdb
and what devices/browsers they are using
◦ This can help us to better optimise the site and to ensure we
test across the most popular platforms
◦ The majority of sessions on GtoPdb come via organic search
(Google) and are performed predominantly from desktop
devices. Chrome is also the browse of choice

15. Acquisition data, Apr 2018 - Mar 2019

16. Browser and Device Category of session,
Apr 2018 - Mar 2019

17. File download statistics
Count
2017-2018 2,810
2018-2019 2,704
Change -3.77%
2017-2018 2018-2019 Change
Targets CSV/TSV file 1084 1085 no change
Interactions CSV/TSV file 345 352 2%
Ligands CSV/TSV file 250 254 1.6%
UniProt Mapping file 165 170 3%
HGNC mapping file 98 118 20%
Peptides CSV file 99 121 22%
PostgreSQL* 160 227 41%
Generic slides (PPT & PDF) 234 196 -16%
Generic poster 104 75 -27%
Other files
Tutorial 492 472 -4%
Terms and Symbols 285 285 no change

18. Web services statistics
◦ Tracking of our web-services has been in place since March 2017
◦ Calls to the web-service are generally from client computers to our server
and are not recorded in the same way as visits to our website
◦ Therefore, we can’t report details on specific users, such as location or
number of visits; only record the number of hits for each distinct URL
◦ There were approximately 105,000 total hits over the year, an increase of
around 13% on the previous period
◦ Calls to target and ligands saw a reduction, but we note an increase in calls
to interaction data and ligand similarity
◦ There was also a large increase in web service calls for ligand substructures,
diseases and database links

19. New features and developments
Web services: As part of the development of the
GtoImmuPdb we have added target and ligands of
immunological relevance, as well as the new
immunopharmacology data types to our web services
Renewal of supplier links: Already mentioned
Converting to HTTPS: Using HTTPS (secure connection) on
websites is becoming increasingly important (browsers and
search engines are starting to warn users when they access
an insecure site). Working with UoE Information Services,
this is now at the final stage of implementation
ChEMBL target links: We have updated all our outgoing
target links to ChEMBL based on the most recent ChEMBL
release (ChEMBL 25)
Switch to using Chemicalize Pro (ChemAxon): A key feature
of the IUPHAR Guide to Pharmacology website is the ability
to perform searches by chemical structure
(http://www.guidetopharmacology.org/GRAC/chemSearch.js
p). The chemical structure search tool utilises Marvin JS by
ChemAxon. In the 2019.1 release we have updated the API
control to use Chemicalize Pro
(https://pro.chemicalize.com/). This update simplifies the
integration of Marvin JS into our website
Update CDK libraries: We have updated the Chemical
Development Kit (CDK) library to version 2.2. This is used by
the Guide to Pharmacology to calculate molecular properties
of ligands curated in the database. As part of this update, we
performed a re-calculation of all molecular properties in the
database
Endogenous ligands: A new download file has been made
available on our downloads page. This file contains a list of
all ligands marked in the database as endogenous or natural
ligands for a given target
Transduction mechanisms: We have undertaken curatorial
work to consolidate our curated data on GPCR transduction
mechanism. In some cases, the database contained
inconsistent data between the transduction mechanism data
on a targets detailed view and its concise view. Our analysis
identified these cases and we’ve put in place curatorial
protocols to fix
Page Navigation: We have updated our web-pages to
feature a drop-down navigation bar, which is revealed when
users scroll-down on longer pages. Many pages on GtoPdb
are quite long, particularly detailed targets pages (e.g. CB1
receptor) – the new drop-down menu keeps key menu
items, and most importantly the site search, in focus at all
time

20. GtoPdb Navigation
Drop-down
navigation bar
keeps search and
help accessible
Return to top
quick-link useful
on long detailed
view pages

21. RDF
We continue to keep the RDF version of the Guide to
Pharmacology up-to-date at each release.
We have implemented an ‘early-stage’ SPARQL endpoint that uses
LodeStar as the web-application layer on top of the triple store.
This provides a graphical frontend to the RDF data and allows
control over SPARQL queries and provides the data in a human-
readable format. This can be accessed at
http://rdf.guidetopharmacology.org/

22. RDF

23. RDF

24. Content
expansion and
updates

25. Entity growth
◦ New entities are being added via Subcommittee updates and the population
of GtoImmuPdb/GtoMPdb, and curator literature trawling
◦ Significant curation effort goes towards tagging pre-existing targets and
ligands with comments and references to GtoImmuPdb and GtoMPdb
Oct
2013
Oct
2015
April
2016
Oct
2016
Apr
2017
Oct
2017
May
2018
Sep
2018
Mar
2019
Target protein IDs 2485 2761 2775 2794 2808 2825 2872 2880 2920
Ligands total 6064 8024 8400 8674 8872 8978 9251 9405 9662
Approved drugs 559 1233 1273 1291 1322 1334 1364 1386 1421
Antibodies 10 138 172 205 212 223 240 248 255
Peptides 1776 1981 2007 2039 2063 2079 2092 2100 2122
Synthetic small
molecules
3504 5055 5363 5563 5729 5807 6048 6180 6401
PubChem SIDs 3107 8024 8328 8674 8831 8978 9251 9405 9662
PubChem CIDs 2694 6057 6163 6337 6813 6822 7109 7224 7407
Binding constants 41076 44691 45534 45908 46287 46488 47058 47426 48071
References 21774 27880 29247 30251 31239 31733 33245 34382 35723

26. Target updates
GPCRs:
Acetylcholine receptors (muscarinic)
Adenosine receptors
Bradykinin receptors
Cannabinoid receptors
Chemokine receptors
Class Frizzled GPCRs
Leukotriene receptors
Lysophospholipid (LPA, S1P) receptors
Metabotropic glutamate receptors
Neuromedin U receptors
Neuropeptide S receptor
Parathyroid hormone receptors
Prostanoid receptors
Proteinase-activated receptors
Somatostatin receptors
Tachykinin receptors
Channels:
Aquaporins
Piezo channels
Transient Receptor Potential channels
Voltage-gated calcium channels
Voltage-gated sodium channels
NHRs:
Androgen receptor
Farnesoid X receptor
Retinoic acid-related orphans
Retinoid X receptors
Enzymes:
Endocannabinoid turnover
Histone deacetylases (HDACs)
Histone demethylases
Fatty acid amide hydrolase (FAAH)
Sugar phosphatases
Dioxygenases
Oxidoreductases
Janus kinase (JakA) family
Carbonic anhydrases
Cytochrome P450s
Adenylyl cyclases (ACs)
Sphingosine kinases
Cyclooxygenases
2-Acylglycerol ester turnover
Eicosanoid turnover
Other protein targets:
Immune checkpoint proteins
CD molecules
Heat shock proteins
Non-catalytic pattern recognition receptors
STAT transcription factors

27. New targets
(not including Antimalarial targets):
◦ Poly ADP-ribose polymerases
◦ Prolyl hydroxylases
◦ Carbonic anhydrases
◦ Paraoxonases
◦ Vanin 1
◦ AQP11
◦ NRF2
◦ CA IX
◦ KIR3DL2 (CD158K)
◦ AC10 (adenylyl cyclase 10)
◦ αβ-Hydrolase 12
◦ PVRIG
◦ C-type lectin domain family 12 member A

28. Relative target growth and coverage
◦ This can be assessed by comparing our own UniProt Human Swiss-Prot cross-
references for targets with quantitative interactions against the other major
chemogenomic resources that also have such cross-references; DrugBank,
BindingDB and ChEMBL

29. ◦ The stats for the 2019.2 release (with 2018.4 in brackets) are as follows
(N.B. because the NCBI Entrez system suffers from overload the links
below may time out but should eventually return the result).
◦ Substances (SID) that we submit to PubChem (refreshing previous
submissions) are up to 9670 (9251).
◦ Those that have defined chemical structures are merged into 7478 (6969)
Compound Identifiers, CIDs (i.e. small molecules and moderate peptides)
◦ The select "IUPHAR/BPS Guide to PHARMACOLOGY"[SourceName] AND
approved [Comment] now retrieves 1518 SIDs (1457) .
◦ Of these 1328 (1278) have CIDs (use the “Find Related Data” operator and select
“same CIDs”.
◦ Of our SIDs, 1151 (993) are tagged in GtoImmuPdb and 282 (258) of these are
approved drugs
◦ Of our CIDs 724 are tagged in GtoImmuPdb
◦ Of our SIDs, 57 are tagged in GtoMPdb and 19 of these are approved drugs
◦ Of our CIDs 51 are tagged in GtoMPdb
◦ We have 1817 (1675) structures that ChEMBL23 does not have, 5456 not in
DrugBank and 6151 not in DrugCentral.
◦ 182 (95) structures unique to us as a source.
◦ PubChem has released a new interface that expands the indexing and
search functionality for our own entries (see example query beside) but
there are still some minor discrepancies in the exact metrics returned
compared to the Entrez interface.
PubChem statistics

30. Status of core subcommittees
NC-IUPHAR Subcommittee Chairs/Liaisons (>90 subcommittees; ~500 scientists)
G protein-coupled receptors Subcommittees
Arthur Christopoulos and Anthony Davenport (Liaisons for all GPCR subcommittees)
5-Hydroxytryptamine:Nick Barnes; Daniel Hoyer Acetylcholine (muscarinic):Arthur Christopoulos Adenosine: Adriaan Izjerman
alpha1-adrenoceptors: Roger Summers alpha2-adrenoceptors: Mika Scheinin Angiotensin: Sadashiva Karnik
Apelin: Anthony Davenport beta-adrenoceptors: Martin Michel Bile acid: Anthony Davenport
Bombesin: Robert Jensen Bradykinin: Réjean Couture Calcitonin: Debbie Hay, David Poyner
Calcium-sensing: Hans Bräuner-Osborne; Katie Leach Cannabinoid: Roger Pertwee, Allyn Howlett Chemokine: Philip Murphy
Cholecystokinin: Laurence Miller Complement peptide: Peter Monk; Trent Woodruff Corticotropin-releasing factor: Richard Hauger, Frank Dautzenberg
Dopamine: Raul Gainetdinov Endothelin: Anthony Davenport G protein-coupled estrogen receptor: Eric Prossnitz
Formylpeptide family: Richard Ye Free fatty acid: Leigh Stoddart;Nicholas Holliday Frizzled: Gunnar Schulte
GABAB: Bernhard Bettler Galanin: Andrew Gundlach Ghrelin: Birgitte Holst
Glucagon receptor family: Laurence Miller Glycoprotein hormone: Deborah Segaloff Gonadotrophin-releasing hormone: Adriaan Ijzerman
Histamine:Paul Chazot; Rob Leurs Hydroxycarboxylic acid: Stefan Offermanns Kisspeptin: Anthony Davenport
Leukotriene: Magnus Bäck Lysophospholipid (LPA): Jerold Chung Lysophospholipid (S1P): Sarah Spiegel
Melanin-concentrating hormone: Jean-Louis Nahon Melanocortin: Tung Fong, Helgi Schiöth Melatonin: Ralf Jockers
Metabotropic glutamate: Cyril Goudet Motilin: Anthony Davenport Neuromedin U: Gary Willars
Neuropeptide FF/neuropeptide AF: Jean-Marie Zajac Neuropeptide S: Girolamo Calơ Neuropeptide W/neuropeptide B: Anthony Davenport
Neuropeptide Y: Dan Larhammar Neurotensin: Jean Mazella Opioid:Larry Toll
Orexin: Christopher Winrow P2Y: Maria-Pia Abbracchio; Kenneth A. Jacobson Parathyroid hormone: Jean-Pierre Vilardaga
QRFP receptor: Jerome Leprince Platelet-activating factor: Satoshi Ishii Prokineticin: Philippe Rondard
Prolactin-releasing peptide: Helgi Schiöth Prostanoid: Xavier Norel Protease-activated:Nigel Bunnett
Relaxin family peptide: Roger Summers Relaxin-like: Nick Barker Somatostatin: Stephan Schulz
Tachykinin: Susan Leeman, Steven Douglas Trace amine: Janet Maguire Thyrotropin-releasing hormone: Marvin Gershengorn
Urotensin: Hubert Vaudry Vasopressin and oxytocin: Stephen Lolait VIP and PACAP: Joseph Pisegna
Ligand-gatedion channels Subcommittees
John Peters (Liaison for all LGIC subcommittees)
Voltage-gatedion channels Subcommittees
Joerg Striessnig (Liaison for all VGIC subcommittees)
Nuclear hormone receptors Subcommittees
John Cidlowski and Thomas Burris (Liaisons for all NHR subcommittees)
5-HT3: John Peters
Acid-sensing (proton-gated) ion channels (ASICs): Stephan Kellenberger
Epithelial sodium channel (ENaC): Israel Hanukoglu
GABAA: Richard Olsen
Glycine: Joseph Lynch
Ionotropic glutamate: Graham Collingridge
Nicotinic acetylcholine: Neil Millar
P2X: Charles Kennedy; Michael Jarvis
ZAC: Paul Davies
Antibodies Subcommittee
Alex Phipps; Michael Spedding
Adenylyl cyclases Subcommittee
Carmen Dessauer
Drug Target and Chemistry Curation Subcommittee
Christopher Southan
Calcium-and sodium-activated potassium: Leonard Kaczmarek
CatSper and Two-Pore: Dejian Ren
Cyclic nucleotide-regulated: Martin Biel
Inwardly rectifying potassium: Paul Slesinger
Transient Receptor Potential: Haoxing Xu
Two-P potassium: Steven Goldstein
Voltage-gated calcium: William Catterall
Voltage-gated potassium: Lily Jan
Voltage-gated sodium: William Catterall
‘Gasotransmitters’ Subcommittee
Andreas Papapetropoulos and Csaba Szabo
Guanylyl cyclases Subcommittee
Adrian Hobbs and Scott Waldman
Non-coding RNAs Subcommittee
Andrew Baker
NHR subcommittees under review
Epigenetics and Kinase Subcommittee
Doriano Fabbro
Pattern Recognition Receptors Subcommittee
Clare Bryant
Proteases and Hydrolases Subcommittee
Christopher Southan
Transporters Subcommittees
Stephen Alexander (Liaison for all Transporter subcommittees
Data Interoperability Subcommittee
Alasdair Gray
Concise Guide to PHARMACOLOGYEditors
Stephen Alexander, Eamonn Kelly, John Peters

31. GPCRs
Liaisons: Arthur Christopoulos and Anthony Davenport
Updates since October 2018
Acetylcholine receptors (muscarinic), Adenosine receptors,
Bradykinin receptors, Cannabinoid receptors, Chemokine
receptors, Class Frizzled GPCRs, Leukotriene receptors,
Lysophospholipid (LPA, S1P) receptors, Metabotropic glutamate
receptors, Neuromedin U receptors, Neuropeptide S receptor,
Parathyroid hormone receptors, Prostanoid receptors,
Proteinase-activated receptors, Somatostatin receptors,
Tachykinin receptors
Ongoing major revision
Acetylcholine receptors (muscarinic), Bradykinin receptors,
Somatostatin receptors
New Subcommittee,
Chairpersons, Members
Réjean Couture (Bradykinin) is joined by Fernand Gobeil, Peter
Monk (Complement peptide) is replaced by Trent Woodruff
Problem areas
Birgitte Holst (Ghrelin), Jean Marie Zajac (NPFF/AF), Dan
Larhammar (NPY), Satoshi Ishii (PAF), Joseph Pisegna
(VIP/PACAP)

32. VGICs
Liaison: Jörg Striessnig
Family Subcommittee Chair Required
CatSper and Two-Pore channels Dejian Ren Review/update
Cyclic nucleotide-regulated channels Martin Biel Review/update
Calcium- and sodium-activated potassium channels Leonard Kaczmarek Review/update
Inwardly rectifying potassium channels Paul Slesinger Review/update
Two P domain potassium channels Steve Goldstein Review/update
Voltage-gated potassium channels Lily Jan Review/update
Ryanodine receptors Isaac Pessah (UC Davis) NEW!
Transient Receptor Potential channels Haoxing Xu Review/update
Voltage-gated calcium channels Jörg Striessnig Review/update
Voltage-gated proton channel Thomas DeCoursey (Rush U) ?
Voltage-gated sodium channels Bill Catterall Review/update

33. LGICs
Liaison: John Peters
Family Subcommittee Chair Required
5-HT3 receptors John Peters, Tim Hales Review/update
Acid-sensing (proton-gated) ion channels
(ASICs)
Stephan Kellenberger, Lachlan Rash Review/update
Epithelial sodium channel (ENaC) Israel Hanukoglu Review/update
GABAA receptors Werner Sieghart Review/update
Glycine receptors
Joseph Lynch, Lucia Sivilotti, Trevor
Smart
Review/update
Ionotropic glutamate receptors Review/update
IP3 receptor Review/update
Nicotinic acetylcholine receptors Neil Millar Review/update
P2X receptors Charles Kennedy, Michael Jarvis Review/update
ZAC Paul Davies, Anders Jensen Review/update

34. NHRs
Liaisons: John Cidlowski and Tom Burris
Family Contact Liaison Required
1A. Thyroid hormone receptors Douglas Forrest John Cidlowski Review/update
1B. Retinoic acid receptors Tom Burris Review/update
1C. Peroxisome proliferator-activated receptors Tom Burris Review/update
1D. Rev-Erb receptors Tom Burris Review/update
1F. Retinoic acid-related orphans Anton Jetten John Cidlowski Review/update
1H. Liver X receptor-like receptors Donald McDonnell John Cidlowski Review/update
1I. Vitamin D receptor-like receptors J. Wesley Pike, Sylvia Christakos John Cidlowski Review/update
2A. Hepatocyte nuclear factor-4 receptors Frances Sladek John Cidlowski Review/update
2B. Retinoid X receptors Tom Burris Review/update
2C. Testicular receptors Tom Burris Review/update
2E. Tailless-like receptors Tom Burris Review/update
2F. COUP-TF-like receptors Sophia Tsai, Ming-Jer Tsai John Cidlowski Review/update
3B. Estrogen-related receptors Tom Burris Review/update
4A. Nerve growth factor IB-like receptors Tom Burris Review/update
5A. Fushi tarazu F1-like receptors Tom Burris Review/update
6A. Germ cell nuclear factor receptors Tom Burris Review/update
0B. DAX-like receptors Tom Burris Review/update
Steroid hormone receptors John Cidlowski Review/update
3A. Estrogen receptors Kenneth Korach, Laurel Koons John Cidlowski Review/update
3C. 3-Ketosteroid receptors (Androgen receptor ) Nancy Weigel John Cidlowski Review/update
3C. 3-Ketosteroid receptors (Glucocorticoid receptor) Robert Oakley, Derek Cain John Cidlowski Review/update
3C. 3-Ketosteroid receptors (Mineralocorticoid receptor) Peter Fuller, Morag Young John Cidlowski Review/update
3C. 3-Ketosteroid receptors (Progesterone receptor) Dean Edwards John Cidlowski Review/update

35. Additional new subcommittee chairs
Endocannabinoid turnover – Patrick Doherty and Christopher
Fowler are replaced by Mario van der Stelt (Leiden) and Jürg
Gertsch (Bern)

36. CGtP 2019/20

37. CGtP 2017/18

38. CGtP 2019/20 planning
Editorial Stage
15 September 2018 Deadline for editors to agree any formatting changes
30 September 2018
Team start to agree new targets (mostly based on the emails AP
gets informing that targets in their articles aren’t in the
database) – allow some flexibility later on so that we don’t miss
really important new targets = NEW TARGET LOCKDOWN
15-26 October 2018
Editors to be sent PDF templates (via PDF OUTBOX, in shared
folders) to review and add comments before they are sent to
collaborators for updates
1 November 2018 Kick-off at GtoPdb – 1st call for updates
3 January 2019 2nd call for updates
31 January 2019 Deadline for receipt of updates
Publication Stage
8 March 2019
Deadline for updates to be completed in the database (i.e. all
the sections that will be uploaded for the CGtP by the early-May
deadline) = DATABASE LOCKDOWN
8 May 2019
Final full LaTeX version of all chapters to be supplied to Wiley,
alongside introduction section and abstracts for each section
8 May 2019
Full list of Editors and Collaborators (including affiliations and
ORCID IDs) and curators to be sent to Wiley
9 June 2019
Complete set of proofs (including covers and front matter) to be
sent to the Editors for review (subsequent rounds of proofing
will be required)
10 July 2019
Final deadline for corrections. No further revisions to proofs
after this date
9 September 2019
(approximate)
Online publication CGtP 2019/20

39. CGtP 2019/20 - Editorial stage
◦ Editorial deadlines were brought forward by 2 weeks
◦ General guidelines from editors to collaborators were
updated
◦ Email campaign:
◦ A PDF file of the target family summary page that has been
generated from the online summary view
◦ General Guidelines for providing the update, including instructions
on how to annotate the attached PDF file using Adobe Acrobat
Reader
◦ An Excel file for listing the Collaborators who contribute to this
update, and for providing consent to be listed as a Collaborator
◦ 233 updates requested; 172 ‘tangible’ updates received

40. CGtP 2019/20 - Publication stage
◦ Chapter organisation: Reducing from 9 to 7 chapters; one Ion Channels
chapter (‘Voltage-gated’, ‘Ligand-gated’ and ‘Other’)
◦ Recognition of the collaborators: in the form of citations for their
contributions
◦ Collaborators must provide consent at time of submitting updates
◦ Collaborators to be listed against relevant chapter (instead of the ‘Overview’)
◦ Ensuring authorship is transmitted to PubMed, Web of Science and Google Scholar – all of
which can be used by authors to determine their H index
◦ The 2019/20 edition of the ‘Concise Guide’ is set for publication in September
2019
◦ Marketing plan:
◦ Wiley using similar marketing strategy to the successful one employed for the CGtP 2017/18
◦ Mailing lists for printed copies and USBs, also available at conferences and for teaching
◦ Review the list of Pharma companies targeted for marketing; use Clarivate to identify
individual researchers within these companies to target for marketing; noted that print
materials are attractive to industry professionals for data protection reasons
◦ Identify Societies that should be sent print copies

41. IUPHAR Guide to
Immunopharmacology
(GtoImmuPdb)
DEVELOPMENTS AND UPDATE

42. GtoImmuPdb Launch
Official launch in October 2018 in Edinburgh
Full Report and presentations at
https://www.guidetoimmunopharmacology.org/immuno/immuphar2018.jsp
Prof. Tracy Hussell delivered the
Anthony Harmer Memorial Lecture:
Decision-making in lung immunity

43. GtoImmuPdb Portal
Inclusion of CVR
OnLife Interview
Links with
Immunopaedia

44. Immunopaedia
Link between Immunopaedia
Case-Studies and
GtoImmuPdb Ligand and
Targets.
• Immunopaedia mark-up
case studies
• GtoPdb curate these and
feedback
• Links added to GtoPdb
database
• Displayed under
Immunopharmacology tab
on ligand summary page
Promotes education, knowledge and research in Immunology
globally. Official provider for online courses for IUIS

45. Immunopaedia

46. GtoImmuPdb Data
Target Class Targets
(593)
Enzymes 193
Catalytic Receptors 148
GPCRs 100
Other Proteins 99
Ion Channels 39
Transporters 9
NHRs 8
Ligand Type Ligands (1150) Ligand assoc.
To disease
Synthetic Organic 710 236
Approved Drugs 254 191
Peptides 239 44
Antibodies 150 104
Metabolites 37 17
Natural Products 13 4
Inorganic 1
Annotations Targets Ligands
Immunological Processes 3195 979 -
Immunological Cell Types 323 151 -
Diseases 56 / 714 38 407

47. GtoImmuPdb Data

48. GtoImmuPdb Data

49. GtoImmuPdb Data
GtoImmuPdb has higher
representation in Catalytic
Receptor, Other Protein and
(to a lesser extent) GPCR
classes

50. GtoImmuPdb Data
GtoImmuPdb has higher
proportion of antibodies and
slightly higher proportion of
approved drugs.

51. GtoImmuPdb Access
Approx. 1,100 sessions per month, with slightly higher engagement (page/session,
duration) compared to GtoPdb.
6 months: October 2018 – March 2019

52. GtoImmuPdb Future Work
Prepare manuscript on Guide to Immunopharmacology
◦ Aiming at Immunology journals/readers
Continue collaborations with Immunopaedia
Implement disease classification

53. IUPHAR/MMV Guide to
Malaria Pharmacology
(GtoMPdb)
DEVELOPMENT

54. GtoMPdb Development
Development builds on robust existing database schema and web-
application code.
Able to produce a new portal by following method used in
generation of the Guide to Immunopharmacology.

55. GtoMPdb Portal
www.guidetomalariapharmacology.org
• Panels provide tailored routes
for browsing antimalarial
data:
• Ligands
• Targets
• Parasite Lifecycle Stages
• Target Species
• The same categories can be
accessed from the menu bar
• Search (top right) is across
GtoPdb and up-weights
antimalarial data

56. GtoMPdb Ligand List
• At present there are two
categories:
• The ‘Antimal’ tab
provides a discrete list
of all ligands that have
the GtoMPdb tag
• Approved tab
• The ‘Antimal’ tab is also
available on other Ligand
List pages

57. GtoMPdb Detailed Target Page
• Modelled on GtoPdb
Detailed Target page
• Shows all curated
information that our
database holds about the
target
• Includes links to PlasmoDB,
UniProt and where
available PDB
PfPNP (ID: 3077)
www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForw
ard?objectId=3077

58. GtoMPdb Detailed Target Page
New comments section
for information of
particular relevance to
malaria
Interactions table
includes Whole
Organism Assay data

59. Parasite Lifecycle Stage
malaria_stage
name
description
malaria_stage2interaction
interaction
• Two new database tables to describe parasite lifecycle stages and link to interaction
data
• New functions in curators submission tool to indicate malaria lifecycle stage

60. Parasite Lifecycle Stage
malaria_stage
name
description
malaria_stage2interaction
interaction
• Two new database tables to describe parasite lifecycle stages and link to interaction
data
• New functions in curators submission tool to indicate malaria lifecycle stage

61. Parasite Lifecycle Stage
malaria_stage
name
description
malaria_stage2interaction
interaction
Target/Ligand counts
build on work from
GtoImmuPdb
Display of interactions uses code
from detailed target pages/ligand
summary pages

62. Target Species Pages
Added description to species information,
extending submission tool to capture
Each Plasmodium strain is stored in the
database as though a different species
Interactions can then be annotated against
specific species/strain
The code can consolidate all data for a
single species for display based on internal
species ID

63. Target Species Pages
Individual Species page
Display of interactions uses code
from detailed target pages/ligand
summary pages
New species description displayed
at top of page. Species comment
displayed in strain specific pop-up

64. GtoMPdb Search
Site-search covers curator comments for targets and ligands
Recently added parasite lifecycle stage names and descriptions
plus target species names and abbreviations
Search produced weighted results if executed from the GtoMPdb
URL
Results with relevance to Malaria Pharmacology up-weighted
Next:
• Add in advanced options, to filter search on targets/ligands
• Incorporate assay descriptions
• Continue testing

65. GtoMPdb Future Work (Dev)
• Currently capturing detailed information within comments
• Extend the database to have specific fields for these data
• Good for search, web-services, analysis…
• Examples:
• Target Candidate Profile (TCP)
• Parasite Reduction Ratio (PRR)
• Parasite Clearance Time (PCT)

66. GtoMPdb Future Work (Dev)
• Advanced Search
• Review data captured in comments – is there anything we could
store in discrete fields, e.g. Target Candidate Profiles (TCP).
• Web Services – we need to add Malaria Pharmacology data to the
API

67. IUPHAR/MMV Guide to
Malaria Pharmacology
(GtoMPdb)
CURATORIAL ASPECTS

68. Collecting & Prioritising Content
•Lists of antimalarial ligands and Plasmodium targets were collated during the pilot
phase
•We have continued to add to these lists and refine priorities
•MMV have provided a list of high priority targets and advised on our pilot ligand list
•EAC feedback
•In addition, we use reference manager software to collect and precurate publications
•Chris has collected over 200 publications that he has tagged with antimalarial specific
tags

69. Content Expansion
• Steady growth in the number of antimalarial ligands and Plasmodium targets
• Our most recent database release (2019.2) contains:
• 57 ligands tagged as in GtoMPdb
• 25 targets tagged as in GtoMPdb
• Our curated ligands include antimalarial leads, drugs in preclinical and clinical
development and approved medicines

70. Content Expansion
GtoPdb:Target Name GtoPdb:Target Name
PfATP4 PfPI3K
PfCARL PfPI4K
PfCPSF3 PfPKG
PfDHFR-TS PfPMX
PfDHODH PfPN
PfDXR PfPPPK-DHPS
PfeEF2 PfSHMT
PfGWT1 PfKRS1
PfHDAC1 PfcPheRS
PfHDP PfPRS
PfHT PfThrRS
PfIspD PfV-type proton ATPase
PfNMT

71. Next Steps
• Curation:
• Complete curation of targets from MMV’s priority list – we will exceed the
number evaluated at the beginning of the project
• Continue curation of ligands – we will meet the number evaluated at the
beginning of the project
• Outreach:
• Press release to coincide with World Malaria Day 2019
• Poster presentation, BioMalPar XV: Biology and Pathology of the Malaria
Parasite, May 2019
• Poster presentation, Edinburgh Infectious Diseases Annual Symposium, June
2019
• Portal development:
• Improvements raised from user feedback
• Extend the database to capture data that is currently in malaria comments
section

72. Next Steps
• Currently capturing detailed information within comments
• Extend the database to have specific fields for these data
• Good for search, web-services, analysis…
• Examples:
• Target Candidate Profile (TCP)
• Parasite Reduction Ratio (PRR)
• Parasite Clearance Time (PCT)

73. Acknowledgements
All past and current members of NC-IUPHAR
NC-IUPHAR subcommittees and Concise Guide to PHARMACOLOGY
editors/contributors
Database team:
◦ Jamie Davies (Principal Investigator)
◦ Joanna Sharman and Simon Harding (Developers)
◦ Adam Pawson, Jane Armstrong, Elena Faccenda, Christopher Southan (Curators)
◦ Tony Wigglesworth (Administrator)
All past and current NC-IUPHAR and website sponsors
Funders: