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Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Archive, Mine, Collaborate®
Community-Based Collaborative Drug Discovery (CDD) for Neglected Infectious Diseases
Collaborative Drug Discovery, Inc.Barry A. Bunin PhD, CEO & President
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
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
Save lives
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
• Archive– 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
Collaborative Drug Discovery
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Archives data
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD can be used for Mining data
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD is Secure & Simple
• 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• Export all data to Excel with SMILES, SAR, & png images
https://www.collaborativedrug.com/pages/privacy_and_security
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD is facilitating Collaborations
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.)
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD aids Collaborations
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Malaria Case Study #1: UCSF/Lipinski/ Cape Town
Testimonial: “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, PhDPfizer, Retired
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Prof. McKerrow’s Network:2000 protease inhibitors, >15 collaborations
Roush groupvinyl sulfones
vinyl sulfonatesepoxides
sulfonamidesphosphononamides
phosphonates
Jon EllmanU.C. Berkeley
hydroxymethylketones
Arquleα-ketoamides
Prototekpeptidomimeticswith heterocyclic
trappinggroups
Kelly ChibaleU. of Capetown
thiosemicarbazones,isatins
GSK(Scott Thompson)
2-propanonesacylhydrazines
Celera(Jim Palmer)
vinyl sulfones
Cohen Groupchalconesacylamides
dihydrazides
L. tropica screen withInstitute Pasteur
collaboration
L. major(cat B)(cat L)
T. brucei(cat B)(cat L)
L. mexicana(cpb)(cpc)
(Mottramcollaboration)
P.falciparum(falcipain)
T. cruzi(cruzain)
L. donvani screen
Prof. McKerrow’s Collaborative Network
Walter Reed(WRAIR)quinolines
thiosemicarbazonesWarner Lambert200,000 diverse
Compound library
McKerrow Compounds
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.© 2007 Collaborative Drug Discovery, Inc.
CDD creates a unique R&D Network
Hub Consortium
Neglected Disease Research Community
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Malaria Case Study #2: St. Jude CRH, Walter Reed, & UNC
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
• Topic: Malaria• Connections
Kip Guy, St. JudeMalaria biology, screening
Alex Tropsha Lab, UNCComputational 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
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Army Malaria Animal Data from WWII from dozens of collaborations and >12K hand drawn compounds
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
A Tropsha Group in Silico Protocol Example in CDD
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
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• Results:
– More than 300 acceptable QSAR classification models.– True negative:83.7% – True positive: 72.4%– Total prediction accuracy: 81.4%
More details see Professor Alex Trophas’ presentations
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
• Topic: Malaria• Connections
Phil Rosenthal, UCSFMalaria biology, screening
Bradley Laboratory, DrexelSynthetic Chemistry
Malaria data, global
Rajarshi Guha, Indiana UniversityDocking to pre-filter Ugi Library
CDD Case Study #3: Bradley-Guha-Rosenthal-CDD
Goal: Accelerate drug discovery for malaria
Bunin, Ekins etc Community Facilitators
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Drexel-UCSF Malaria Data Set within the Context ofOther CDD Community Neglected Disease Data Sets
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Useful Chemistry Ugi Compound in CDD (public login: usefulchemistry, Password: cddcdd)
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Ugi-4CC Product tested in P. Falciparum Cell Assay is captured in the CDD Database
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Open Access Data Easily Exported from CDD Database
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Case Study #4: Mining Capabilities between Groups (Ballel vs. TAACF)
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Mining Capabilities between Groups (Ballel vs. Known Drugs)
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Collaborative Capabilities: Securely View and Analyze Data Sets
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Case Study #5: GPCR Ki Database from Roth PDSP site
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Archive – Protocols: Roth Ki Database
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Mining the Roth data
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
95% Use Private Groups: My Personal Example
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Mining Plugin can show LogD
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Mining Plugin can show molecule 3D View
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD allows data Export
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Why is CDD and our collaborators doing this?
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
For Drug Discovery, Collaborative software can make a difference
• CDD solves complex drug discovery software and data needs
– Balancing openness with user choice
– Efficiencies of integrated specialization balanced with end-user choice for access to sensitive drug discovery data
• Metcalfe’s law and Moore’s law
• CDD for other discovery data: drug, medical, & clinical research
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD – Community Open Access Data
1. Dr. Christopher Lipinski (ex-Pfizer)Chemoinformatics data on FDA and Orphan approved drugs
2. Prof. Roos (U. Penn)Modern Malaria literature data linked to genes
3. Prof. Gelb (UW)Modern Malaria literature data linked to assays
4. Prof. Guy (St. Jude CRH)>12,000 Army Malaria screening data dating back to WW-II after escrow
period5. Prof. McKerrow (UCSF)
“Open-Content” Drug discovery – T. Brucei, T. Cruzi, S. Mansoni, Leishmania, P. falciparum
6. Dr. Shoichet (UCSF)Aggregator- non-aggregator data
7. Dr. Ekins (UMDNJ, U. Maryland, ex-Pfizer/Lilly)Toxicology data
CDD collaborators
And growing….
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Networks Selectively Sharing “Public-Private Partnerships”
# drug discovery possibilities = # of [compounds][targets][indications][experts]
CDD Leverages a network of drug discovery Experts
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Collaborative Road-Map:
CDD can be used to manage public and private collaborators
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD is a growing community scientific community
1. CDD is executing on Geometric Community Growth2. Doubled # in community in last 12 months3. Doubling # in community in next 6 months4. Applications to adjacent markets to scale
collaborative discovery model Any data from excel files, started with SAR
5. CDD best fit for startups, academics, and Foundations
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Acknowledgements
• 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
• …& 100s of collaborators mostly from academia and foundations (some industry)
• Thank you!
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD Current Community & Strategic Relationships
• ASINEX• Broad Institute• Cedars-Sinai Medical Center• Columbia University• Cornell University• Drugs for Neglected Diseases initiative • Eli Lilly & Co.• 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.
Contact: Barry Bunin, PhD, [email protected]
• 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
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Extra slides
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD facilitates drug discovery
• CDD currently helps…
– Discover new medicines faster
– Focus on important neglected disease research
– Empower individuals and develop drugs
– Broadly improve human health and life
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD database system: Security overview
• CDD encrypts all traffic between a user's web browser and our servers once the user has logged in.
• CDD does thorough automated testing of our application code, including security tests to make sure one group cannot access another group's private data.
• CDD uses two levels of firewalling ("defense in depth"), hardware and software, for each sensitive server in our server environment.
• CDD encrypts all database and customer file backups using public key cryptography, and the private keys are backed up securely.
• CDD stores user passwords in our database using strong, one-way encryption hashes. • CDD stays current with all security updates to our system software, firmware and
operating systems. • CDD uses Linux systems in production. • A number of application security enhancements around password security are being
made mandatory. • Access to production servers and superuser accounts is limited and audited within CDD.
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
CDD chemical and biological data with 3rd party models
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
Where CDD Community is Today
and Where Is It Going Tomorrow?
Archive, Mine, Collaborate© 2007 Collaborative Drug Discovery, Inc.
QSAR Models Based on anti-P. falciparum Activity
• A library of 3133 compounds screened for anti- P. falciparumactivity from Dr. Guy.
• 158 compounds were selected as active.• QSAR kNN (k-nearest neighbor) models developed based on
158 hits + 271 inactive compounds (selected from the whole library) = 429.
• The selected 271 inactive compounds covered most of the chemical space.
Red: selected inactive; Purple: unselected inactive in the whole library.