A NEW COLLABORATIVE WEB-BASED DATABASE ARCHITECTURE FOR COMMUNITY- BASED PHARMACEUTICAL RESEARCH

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Archive, Mine, Collaborate

®

A NEW COLLABORATIVE WEB-BASED

DATABASE ARCHITECTURE FOR COMMUNITY-

BASED PHARMACEUTICAL RESEARCH

Collaborative Drug Discovery, Inc.

Sean Ekins PhD, DSc.

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Using

CDD

can save time, money and improve discovery

• Promote discoveries that would

not otherwise happen.

• Utilize limited resources more

effectively.

• Accelerate the discovery of

effective treatments for neglected

infectious diseases.

Save time

Save money

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• –

Organize and upload your experimental data

• Mine

–

Analyze your data to suggest new drug candidates

–

Helps advance promising drugs

• Collaborate

–

Keep your data 100% private,

–

Exchange confidentially

with collaborators,

or

…

–

Share openly within the CDD community

–

Publications, collaborations, peer recognition

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CDD chemical and biological data

with 3

rd

_{party models}

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CDD A

rchives data

Traditional databases

Excel and other spreadsheets

A modern database

Web-based

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CDD

is

S

ecure &

S

imple

• Web based (log in securely into to your database from any computer

using any common browser – Firefox, IE, Safari)

• Hosted on remote server (lower cost)

• Highly secure, all traffic encrypted, server in a secure professionally

hosted environment

• Automatically backed up nightly

• Uses

JChemBase software with Rails via a Ruby-Java bridge,

(structure searching and inserting/ modifying structures)

• Marvin applet for structure editing

• Export all data to Excel with SMILES, SDF, SAR, & png images

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CDD

is facilitating

C

ollaborations

1. Malaria Chemosensitizers (Cape Town, UCSF, Lipinski)

2. Malaria Computational and Experimental around largest set of historical

small molecule animal SAR data (UNC, St. Jude)

3. Malaria UGI-4CC Open Collaboration (Drexel-UCSF)

4. Tuberculosis Public Private Partnership Examples (TAACF, Lilly, Cornell)

5. GPCR Ki Database (PDSP, UNC)

6. Many Others (company working on PI3 Kinase for Cancer, vendor with

commercial compounds, etc.)

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CDD

aids global malaria

C

ollaborations

Result

New leads reveal known

drugs that reverse

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CDD

Malaria Case Study #1:

UCSF/Lipinski/ Cape Town

“One of the biggest barriers for academic drug discovery is the

poor access to chemical data represented in an intelligent

format. CDD presents data and associated tools that capture

the relationship between chemical structure and biological

activity. Structure-Activity Relationship (SAR) data substantially

improve the distributed drug discovery process.”

— Christopher Lipinski, PhD

Pfizer, Retired

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CDD

creates a unique

R&D Network

Hub Consortium

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CDD C

ollaborative Capabilities:

Securely View and

A

nalyze Data Sets

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CDD Malaria Case Study #2:

St. Jude CRH, Walter Reed, & UNC

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• Topic: Malaria

• Connections

Kip Guy, St. Jude

Malaria biology, screening

Alex Tropsha Lab, UNC

Computational Chemistry, informatics

Malaria data, global

Liying Zhang Hao Zhu

Tropsha-Guy-CDD Malaria Computational-

Experimental Collaboration

Goal: Accelerate computational drug discovery for malaria

Bunin, Ekins etc

Facilitators

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Army Malaria Animal Data from WWII from dozens of

collaborations and >12K hand drawn compounds

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QSAR Models have high prediction accuracy

• 70 compounds in the 429 compounds were randomly selected as

external validation set.

• QSAR kNN

(k-nearest neighbor)

models with Dragon descriptors

• Results:

–

More than 300 acceptable QSAR classification models.

–

True negative:83.7%

–

True positive: 72.4%

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Open Access Data Easily

Exported from

CDD

Database

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CDD Case Study #3: Mining Capabilities

between Groups (Ballel vs. TAACF)

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M

ining Capabilities between

Groups (Ballel vs. Known Drugs)

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Where is the CDD Community Today

& Where is it Going Tomorrow?

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Total World Spending on Drug Discovery,

Collaborative software can make a difference

Large Markets:

–

$28 Billion/year NIH budget funding over 2800 institutions

–

$58.8 Billion/year Biopharmaceutical R&D spending

(

http://www.phrma.org/

)

–

$16 Billion in grants to date just from Gates Foundation alone

Enable Economics of Specialization:

• CDD solves complex drug discovery software and data needs

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CDD Collaborative Road-Map:

CDD can be used to manage public

and private collaborators

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CDD

is a growing community scientific community

1. CDD is executing on Geometric Community Growth

2. Doubled # in community in last 12 months

3. Doubling # in community in next 6 months

4. Applications to adjacent markets to scale

collaborative discovery model

Any data from excel files etc.

5. CDD ideal for startups, academics, and foundations

Coming Soon: Private-to-Private Collaborative features, and

web2.0 social networking features

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Acknowledgments

• Moses Hohman, PhD

(Director Software Engineering)

• Northwestern Assoc. Director of Bioinformatics, Thoughtworks, Inc., U of

Chicago (PhD), Harvard (

magna cum laude, Physics)

• Sylvia Ernst, PhD

(Director Community Growth)

• Accelrys-Scitegic, MDL-Elsevier-Beilstein

• Kellan Gregory

(CDD Community Interests

)

• Tufts University

• Peter Cohan

(BOD)

• Symyx (VP Bus Dev & President-Discovery Tools), MDL (VP Customer

Marketing),

www.secondderivative.com

, author.

• Alpheus Bingham, PhD

(BOD)

• Lilly, eLilly, Innocentive

• Omidyar Network, Founders Fund, ChemAxon, ASINEX

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CDD Current Community

& Strategic Relationships

• ASINEX

• Broad Institute

• Cedars-Sinai Medical Center

• Columbia University

• Cornell University

• Drugs for Neglected Diseases initiative

• Fred Hutchinson CRC

• Harvard University

• Indiana University–Purdue University Indianapolis

• Johns Hopkins

• Louisiana State University

• Marine Biological Laboratory

• MIT

• Myelin Repair Foundation

• San Francisco VA Medical Center

• Seattle Biomedical Research Institute

• Semafore Pharmaceuticals, Inc.

•

• www.collaborativedrug.com

• Stanford University

• St. Jude Children’s Research Hospital

• UCSF General Hospital

• University of California, Berkeley

• University of California, Los Angeles

• University of California, San Francisco

• University of California, Santa Cruz

• University of Cape Town

• University of Mississippi

• University of North Carolina

• University of Pennsylvania

• University of Sydney

• University of Texas

• University of Washington