A presentation by Professor Tim Gallagher, University of Bristol - given at the Open Science Showcase held by the Royal Society of Chemistry on 26 February 2014.

1. The goal: to establish a National Compound
Collection capitalising on UK Academic Chemistry
What is a “national compound collection”?
How would it differ from existing collections?
What has driven this project?
What are we doing now?
Where can this go in the future?
Opportunities and downstream challenges
David Fox (RSC), Paul Edwards (Scicate Ltd),
Joe Sweeney (UoHuddersfield), Tim Gallagher (UoBristol)

2. What is a “National Compound Collection”?
An in silico structural database; a tangible collection of
novel low-mid range MW entities
Comprises a wide diversity of untapped structural types
Searchable/filterable/data linked to source (synthesis)
UK PhD theses – published resource
Support for all “molecule-dependent” activities
E.g. Bioscience – new “hits” or leads, tools to support
validation of new targets/pathways
Expansion of ‘druggable’ space
New IP; enable UK competitive edge

3. What has driven this project?
On-going drug discovery initiatives/collections
David Fox/RSC ; MRCT; Dundee-led 3D Fragment
consortium; IMI Lead Factory; NIH’s Accelerating
Medicines Partnership
IP: major barrier around physical samples
PhD theses – largely “IP-free”
RSC’s ChemSpider – “in need of a community”
The mood has changed
“Open innovation” model of industrial R&D
Demonstrating “impact” provides a key driver
Opportunity to realize UK taxpayer's role in
chemistry research to provide competitive edge

4. 1. What are we doing now?
RSC-sponsored pilot study; Feb to July ‘14
Define data extraction/deposition methodology
Demonstrate additional value of academic
collection - build communities
15 university partners + British Library
Structural data deposited to ChemSpider; linked
to validated experimental protocols
New and under-exploited structural classes
Enriched in 3-D and chiral molecules
Numerous end-users; bioscience as initial focus

5. 2. What are we doing now?
Pilot collection of 60k; make widely available;
maximise structure variation
Industry and academic bioscience partners
Assess diversity/uniqueness of “structure space”
In silico binding activity against a variety of
important drug targets
Enable re-synthesis for validation
Energise broader-based communities
Plan and then deliver full, national scale activity

6. Where can this go to in the future?
Two components: “legacy” and “going forward”
Engage universities, end-users, funders
Link to e.g. CROs, compound curators, etc
Define a financial sustainable but “open”
mechanism to support transition to national level
Challenges and opportunities
Facilitate translation from virtual to REAL collection
Support breadth of potential user groups/sectors
How “open” can/should access be?
Broader European collaborative opportunity?

7. REAL
COLLECTION
<10K?
Promiscuity
screening
In silico
filters
Compound
re-synthesis and
enrichment of hit
series
Screening
collection
Compound
collation &
curation
Compound
plating &
distribution
UK NCC
TANGIBLE
COLLECTION
ACADEMIC
THESES
Wide Engagement
End-users/CROs,
Funders, RSC
Compare to other
collection to provide
evidence base
In silico
filters
Promiscuity
screening
Where did we start?

8. REAL
COLLECTION
<10K?
Promiscuity
screening
In silico
filters
Compound
re-synthesis and
enrichment of hit
series
Screening
collection
Don’t filter
Leave to end-user
Compound
collation &
curation
Compound
plating &
distribution
UK NCC
TANGIBLE
COLLECTION
ACADEMIC
THESES
Wide Engagement
End-users/CROs,
Funders, RSC
Compare to other
collection to provide
evidence base
In silico
filters
Promiscuity
screening
Where are we now?

9. New targets
New materials
Promiscuity
screening
Screening by industrial
and academic end-users
(bioscience, formulation)
New agrochemicals
New pharmaceuticals
New formulations
NEW business
opportunities
Academia-industry
Collaborations
New academic
interactions
Where could we go to?
UK NCC
TANGIBLE
COLLECTION
RE-SYNTHESIS
Real collection
CRO-based
Compound collation,
curation, plating and
distribution
NEW
ACADEMIC
THESES

11. NIH - Accelerating Medicines Partnership
• Launched 4 Feb 2014
• NIH, 10 biopharma companies and 8 non-profit
organisations
• Aims to transform the current model for developing
new diagnostic and treatments by jointly identifying
and validating promising biological targets
• Initial focus on four disease areas:
– Alzheimer’s disease
– type 2 diabetes
– autoimmune disorders of rheumatoid arthritis and
systemic lupus erythematosus (lupus)