IUPHAR/MMV Guide to Malaria Pharmacology slide set presented by Dr. Jane Armstrong at GEMM 2019, Edinburgh, UK.

1. Introducing the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY:
an expertly curated resource capturing antimalarial compounds and
their Plasmodium targets
Jane Armstrong
Wednesday 11th December 2019
Glasgow-Edinburgh Malaria Meeting

2. OVERVIEW
• Project introduction
• Database content
• Navigating the website
• Future plans

3. INTRODUCTION

4. www.guidetomalariapharmacology.org
• Medicines for Malaria Venture (MMV)
funded project
• Aims:
• Extend the existing Guide to
PHARMACOLOGY database
(GtoPdb) with curated antimalarial
compounds and their Plasmodium
molecular targets
• Provide a new portal that is
optimized for the malaria research
community
Guide to MALARIA PHARMACOLOGY (GtoMPdb)

5. Data on human
drug targets and
potential targets
Recommended
experimental
ligands
Information on
approved drugs
Entry point into
pharmacological
literature
Sources of
further reading
Detailed
annotation for
important targets
Overviews of the
key properties of
target families
Target and
ligand
nomenclature
• The GtoPdb is an open, expert-driven database of pharmacological targets and the substances
that act on them: ~1,700 drug targets, ~9,400 ligands, including ~1,300 approved drugs
• Focus has been on the pharmacology of human non-infectious diseases
• Data are reviewed by an international network of >500 scientists in >100 subcommittees of the IUPHAR
Nomenclature Committee (NC-IUPHAR)
IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

6. DATABASE CONTENT

7. • All data are manually curated from the primary literature with guidance from our committee of
scientific advisors
• Steady growth in the number of antimalarial ligands and Plasmodium targets
• Our most recent database release (2019.5) contains:
• 72 ligands tagged as in GtoMPdb
• 30 targets tagged as in GtoMPdb
• Our curated ligands include antimalarial leads, drugs in preclinical and clinical development and
approved medicines
Content Expansion

8. GtoPdb:Target Name GtoPdb:Target Name
PfATP4 PfPANK1
PfCARL PfPDEalpha
PfCPSF3 PfPI3K
PfCYTB PfPI4K
PfDHFR-TS PfPKG
PfDHODH PfPMX
PfDXR Pfproteasome subunit beta type-5
PfeEF2 PfPNP
PfGWT1 PfPPPK-DHPS
PfHDAC1 PfSHMT
PfHDP PfKRS1
PfHT PfcPheRS
PfIspD PfPRS
PfNDH2 PfThrRS
PfNMT PfV-type proton ATPase
Database Content – Target List

9. NAVIGATING THE WEBSITE
Including key features

10. www.guidetomalariapharmacology.org
• Retains the general layout of the parent site but
includes a number of new features
• Distinct identity with logo, colour scheme and
header bar
• Dedicated domain
• 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
• New Help (under Resources) and About pages
have been provided
First public release (January 2019, beta v1) > Full public release and official launch (September 2019)
GtoMPdb Portal

11. www.guidetomalariapharmacology.org/GRAC/LigandDisplayForward?ligandId=9721
• Modelled on GtoPdb Ligand page
• Shows all curated information that
our database holds about the
ligand
• New features have been
developed for GtoMPdb ligands
cipargamin (ID: 9721)
GtoMPdb Ligand Page

12. cipargamin (ID: 9721)
www.guidetomalariapharmacology.org/GRAC/LigandDisplayForward?ligandId=9721
• Additional curator comments of
relevance to malaria
• Target Candidate Profile (TCP) is
provided where available
• Information about Potential
Target/Mechanism of Action. For
antimalarials this is often unknown
or poorly understood
Malaria Tab
GtoMPdb Ligand Page – new features

13. cipargamin (ID: 9721)
www.guidetomalariapharmacology.org/GRAC/LigandDisplayForward?ligandId=9721
• A new whole organism assay
type has been introduced to
capture data from the whole cell
assays used routinely in
antimalarial drug discovery
• This information is contained in
the interactions table available
on both the Ligand page and
the Detailed Target Page
Whole Parasite Assay Data
GtoMPdb Ligand Page – new features

14. • 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
• New comments section for information of
particular relevance to malaria
PfPNP (ID: 3077)
www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3077
GtoMPdb Detailed Target Page

15. Homepage includes:
• Background section with a short
introduction to the Plasmodium
lifecycle and links to more
detailed resources
• Links to individual page for each
of the 5 top-level Plasmodium
lifecycle stages
Parasite Lifecycle Pages

16. Parasite Lifecycle Pages
Individual Lifecycle Stage page

17. Parasite Lifecycle Pages
Individual Lifecycle Stage page
Section for detailed
description of
lifecycle stage
Total number of
target and ligand
associations
Table providing
complete list of
target and ligand
interactions

18. Homepage includes:
• Background section with a
description of clinical and
experimental relevant species
• Links to individual pages for
species that we have data for in
GtoMPdb
• Resources section
Target Species Pages

19. Target Species Pages
Individual Species page

20. Target Species Pages
Individual Species page
Section for detailed
species description
Total number of
target and ligand
associations
Pop-up window
provides strain
information
Table providing
complete list of
target and ligand
interactions

21. FUTURE PLANS

22. Next steps…
• Main development phase is now complete
• Funding in place to maintain GtoMPdb and expand content
• Curation of ligands will focus on compounds that are at an early stage of development
• User feedback will be used to prioritize content expansion and inform improvements to the portal

23. • Poster session at GEMM2019
• Nucleic Acids Research (Database Issue): article describing current status
The IUPHAR/BPS Guide to PHARMACOLOGY in 2020: extending immunopharmacology
content and introducing the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY. Epub
ahead of print: doi:10.1093/nar/gkz951
• Help page (https://www.guidetomalariapharmacology.org/malaria/gtmpHelpPage.jsp)
• Blog posts (http://blog.guidetopharmacology.org/)
• Follow us on
• Download slides and posters
• Email (enquiries@guidetopharmacology.org)
@GuidetoPHARM
Find out more about GtoMPdb

24. Acknowledgements
• All past and current members of NC-IUPHAR
• IUPHAR/MMV Expert Advisory Committee
• Jeremy Burrows, Brice Campo, Javier Gamo, Stephen Ward (MMV)
• Michael Spedding (IUPHAR)
• Database team:
• Jamie Davies (Principal Investigator)
• Simon Harding and Joanna Sharman (Developers)
• Adam Pawson, Elena Faccenda and Christopher Southan (Curators)
• IUPHAR/MMV Guide to MALARIA PHARMACOLOGY and IUPHAR/BPS Guide to
PHARMACOLOGY funders: