A/Prof Matthew Todd, School of Chemistry, University of Sydney

mattoddchem

http://intermolecular.wordpress.com/

JCBMS, Cambridge, July 14th 2014

Matthew Todd

http://www3.imperial.ac.uk/schisto; http://bit.ly/9azFHv

Open Project #1: Bilharzia

N

N

O

O

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Stepwise vs. Concerted3/26

The Synaptic Leap and Usefulchem4/26

HN

O

N

OO O

N

O

N

OH

catalyst

Industrial Precursor

Praziquantel

Funding and Lab Books5/26

Openness and the Commercial Sector6/26

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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http://bit.ly/dtkwf0, http://bit.ly/aqHWtV, http://bit.ly/bJNZ8N, http://bit.ly/8TrvZ4

Advantages8/26

Transparency Benefits of the Starfish

…but a Need for FoodSpeed

HIT LEAD?

CONVENTIONAL DRUG DISCOVERY

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Great Starting Points11/26

Open Source Malaria12/26

http://www.thesynapticleap.org/node/343

OSM Series Summary13/26

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

SO

NN

N

SN

ClO

O

N

N

N

S

NH2 S NH2

OO

N

N

NN

OF

F

HN O

Cl

SERIES 1Potent

Ester problematic

SERIES 1APotent

Gametocyte activeLow solubility

SERIES 2Potent

Duplication with Closed Group

SERIES 3Potent

Singleton?

SERIES 4Already investigated in Pharma/CRO

Promising PKPossible PfATP4 activity

PARKED ONGOING NEW

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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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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Inputs Last Week

Current

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Metabolic Stability

Current

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Chris Swain

Start of Open Source TB Project

Current

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With Jamie Triccas, Usyd Medicine, and GSK

Tres Cantos

Is Open Source Drug Discovery Realistic?22/26

http://www.fda.gov/scienceresearch/specialtopics/criticalpathinitiative/criticalpathopportunitiesreports/ucm077262.htm

100% Obvious 29% Obvious89% Obvious

Break a Monolithic Structure22/26

Reconstruct22/26

Nimble, self-assembly encouraged through openness

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The Analogy

http://bit.ly/13zFJ6s

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The Analogy

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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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