Why are we still doing industrial age drug
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Why Are We Still Doing Industrial Age Drug Discovery For Neglected Diseases in The Information Age?
Sean Ekins
Collaborations In Chemistry, Fuquay Varina, NC
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Some Technologies change faster than we do
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But Drug Discovery has not changed much in 40 years
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Because change happens slowly
Drug discovery is a very slow race… that needs a kickstart
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And of course no treatments for neglected diseases are blockbusters
Still valuing the 70’s BLOCKBUSTER
model but its changing
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The Old School vs New School screening
• New School - Many hurdles before in vivo -
lots of data Yet HTS started in the 1980’s!!
• Old school – go in vivo at outset – little data
• New database technologies work well for
New school but ..Old School type data ?
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Drug Discovery Archeology
• Still a heavy emphasis on “testing” “doing “ rather than ‘learning’
• Mining data and historic data will increase in value
• Data becomes a repurposing opportunity
• How do we position databases for this?
• What about neglected diseases?
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Now neglected diseases has big data too
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A computational
window into data and
models
Should there be more ?
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But what about small data?
• In some cases its all we have
• In vivo data is not high throughput
• Small data builds networks
V
http://smalldatagroup.com/
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Ponder et al., Pharm Res In Press 2013
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Tested >300,000 molecules Tested ~2M
>1500 active and non toxic Published 177
Big Data: Screening for New Tuberculosis Treatments
How many will become a new drug? How do we learn from this big data?
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«Tuberculosis» 333 papers in PubMed
«Malaria» 301 papers in PubMed
Small data: Mouse In vivo model data
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Can combining Big and Small
data (in vitro, in vivo) help us
find better compounds,
faster ?
Avoid testing as
many molecules
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Connecting data/tools like a TB Spider
In vitro data In vivo data
Target data
ADME/Tox data & Models
Drug-like scaffold creation
TB Prediction Tools TB Publications
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Where are the New TB drugs to be found?
In vivo actives (yellow)
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Optimal Human properties
Optimal Mouse properties
Optimal TB entry properties
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Filling the toolbox
• Who has the data?
• Who has the models?
• Who has molecules? Drug Discovery
Toolbox
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Hunting for the in vivo data It’s out there.. be patient
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30 years with little TB mouse in vivo data
TB
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MoDELS RESIDE IN PAPERS
NOT ACCESSIBLE…THIS IS
UNDESIRABLE
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Hunting High and Low for new molecules to test
We need to search sources..
From the Oceans…
To the ground To the trees To the air.. And do it virtually
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Time for the New New School
Models replace testing
Testing = confirming
Predict in vivo and in vitro in parallel
MULTIDIMENSIONAL
Save resources
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TO BE CONTINUED…
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Joel S. Freundlich
Antony J. Williams
Alex M. Clark