Presentation about the Open Source Malaria group, given by Matthew Todd a the Open Source Pharma Conference, which took place at Rockefeller Foundation Bellagio Center in July 2014.

1. A/Prof Matthew Todd, School of Chemistry, University of Sydney
mattoddchem
http://intermolecular.wordpress.com/
JCBMS, Cambridge, July 14th 2014
Matthew Todd

2. http://www3.imperial.ac.uk/schisto; http://bit.ly/9azFHv
Open Project #1: Bilharzia
N
N
O
O
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3. Stepwise vs. Concerted
3/26

4. The Synaptic Leap and Usefulchem
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5. H
N
O
N
O
O O
N
O
N
O
H
catalyst
Industrial
Precursor
Praziquantel
Funding and Lab Books
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6. Openness and the Commercial Sector
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7. Completed Open Solution
Details of Route: PLoS NTD 2011, 5(9): e1260
Full Description of Project: Nature Chemistry 2011, 3, 745-748
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8. http://bit.ly/dtkwf0, http://bit.ly/aqHWtV, http://bit.ly/bJNZ8N, http://bit.ly/8TrvZ4
Advantages
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Transparency Benefits of the Starfish
…but a Need for FoodSpeed

9. HIT LEAD?
CONVENTIONAL DRUG DISCOVERY
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10. Great Starting Points
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11. Open Source Malaria
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http://www.thesynapticleap.org/node/343

12. OSM Series Summary
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http://openwetware.org/wiki/OpenSourceMalaria:Compound_Series
Series typically not exhausted - Decision points made to move to another.
Anyone free to employ OSM infrastructure to explore these series
F
H2N
N
O
O
O
F
N
HN
N
O
S
O
N
N
N
S
N
Cl
O
O
N
N
N
S
NH2 S NH2
O
O
N
N
N
N
O
F
F
HN O
Cl
SERIES 1
Potent
Ester problematic
SERIES 1A
Potent
Gametocyte active
Low solubility
SERIES 2
Potent
Duplication with Closed Group
SERIES 3
Potent
Singleton?
SERIES 4
Already investigated in Pharma/CRO
Promising PK
Possible PfATP4 activity
PARKED ONGOING NEW

13. Openness Activates the Community
Open Source Drug Discovery – A Limited Tutorial, Parasitology, 2014, 141, 148–157
ONLINE LAB BOOKS DATA MANAGEMENT OPEN PROJECT MANAGEMENT
ONLINE MEETINGSALERT MECHANISMS @O_S_M
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14. 15/26

15. 16/26

16. 17/26

17. Current Focus – Series 4
Current What OSM Needs Now
• Analog design
• Organic synthesis
• Prediction of pharmacophore
• On-call hERG assay
• Data curation/automation
• Contacts at CROs
• Law/Economics of Downstream
Rapid
Parasite
Clearance
in Mice
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18. Inputs Last Week
Current
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19. Metabolic Stability
Current
20/26
Chris Swain

20. Start of Open Source TB Project
Current
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With Jamie Triccas, Usyd Medicine, and GSK
Tres Cantos

21. Is Open Source Drug Discovery Realistic?
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http://www.fda.gov/scienceresearch/specialtopics/criticalpathinitiative/criticalpathopportunitiesreports/ucm077262.htm
100% Obvious 29% Obvious89% Obvious

22. Break a Monolithic Structure
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23. Reconstruct
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Nimble, self-assembly encouraged through openness

24. 24/26
The Analogy
http://bit.ly/13zFJ6s

25. 25/26
The Analogy

26. Sydney: Michael Woelfe, Paul Ylioja, Murray Robertson, Alice Williamson, Mike Robins, Kat Badiola,
Jimmy Cronshaw, Zoe Hungerford, Laura White, Clara Chen, Angela Butera, Matin Dean, Althea Tsang,
Jo Ubels, Tom MacDonald, Ingo Topolnicki, Carmen Tran WHO/TDR: Piero Olliaro Syncom B.V.: Jean-
Paul Seerden MMV: Tim Wells, Paul Willis and Jeremy Burrows GSK: Javier Gamo and Felix Calderon
Southampton: Jeremy Frey and team ChEMBL: John Overington, Iain Wallace, George Papadatos ANU:
Kiaran Kirk Adelaide Dennis and Adele Lehane OSDD India: Sanjay Batra, Soumya Bhattacharyya
Eskitis: Vicky Avery, Sabine Fletcher, Sandra Duffy Monash: Sue Charman, Karen White. Melbourne:
Stuart Ralph, James Pham Basel: Sergio Wittlin Edinburgh: Patrick Thompson, Devon Scott, Eduvie
Omene Stockholm: Sabin Llona Minguez UCSD: Stephan Meister Lawrence Uni: Stefan Debbert Other
Online: Chris Southan, Jonathan Baell, Chris Swain and many others
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27. 26/26
Open Access
Content may be viewed freely without charge to the reader.
Open Innovation
Problems are posted openly, solutions can be closed/private.
Significant level of ownership of result.
Crowdsourcing
A group completes a task by individuals completing small fragments. No
requirement for methods/details to be shared.
Gain: Person-power
Open Source
All data and ideas are shared openly (i.e. with everyone), anyone may
contribute at any level.
All content may be remixed and reused.
No consortia, restrictions, embargoes, minimal ownership.
Gain: Lack of (unnecessary) duplication