Why Are We Still Doing Industrial Age Drug Discovery For Neglected Diseases in The Information Age? Sean Ekins Collaborations In Chemistry, Fuquay Varina, NC
Jan 28, 2015
Why Are We Still Doing Industrial Age Drug Discovery For Neglected Diseases in The Information Age?
Sean Ekins
Collaborations In Chemistry, Fuquay Varina, NC
Some Technologies change faster than we do
But Drug Discovery has not changed much in 40 years
Because change happens slowly
Drug discovery is a very slow race… that needs a kickstart
And of course no treatments for neglected diseases are blockbusters
Still valuing the 70’s BLOCKBUSTER
model but its changing
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 ?
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?
Now neglected diseases has big data too
A computational
window into data and
models
Should there be more ?
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/
Ponder et al., Pharm Res In Press 2013
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?
«Tuberculosis» 333 papers in PubMed
«Malaria» 301 papers in PubMed
Small data: Mouse In vivo model data
Can combining Big and Small
data (in vitro, in vivo) help us
find better compounds,
faster ?
Avoid testing as
many molecules
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
Where are the New TB drugs to be found?
In vivo actives (yellow)
Optimal Human properties
Optimal Mouse properties
Optimal TB entry properties
Filling the toolbox
• Who has the data?
• Who has the models?
• Who has molecules? Drug Discovery
Toolbox
Hunting for the in vivo data It’s out there.. be patient
30 years with little TB mouse in vivo data
TB
MoDELS RESIDE IN PAPERS
NOT ACCESSIBLE…THIS IS
UNDESIRABLE
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
Time for the New New School
Models replace testing
Testing = confirming
Predict in vivo and in vitro in parallel
MULTIDIMENSIONAL
Save resources
TO BE CONTINUED…
Joel S. Freundlich
Antony J. Williams
Alex M. Clark