Science for Life
Drug Discovery Resources at Purdue
Andrew Mesecar, PhD
Deputy Director, Purdue Center for Cancer Research
Walther Professor of Cancer Structural Biology
Department of Biological Sciences and Department of Chemistry
iCTSI - Molecular Therapeutics & Drug Discovery – April 21st, 2014
Center for Cancer Research and Bindley Biosciences Center
Integrating Shared Resources into Drug Discovery at Purdue
Target
Discovery &
Selection
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DNA Sequencing
Proteomics*
Metabolite Profiling*
Transgenic Mouse*
BioInformatics
Hit-2-Lead
Discovery
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Biomol. Screening**
Comp. Chemistry
Medicinal Chemistry
NMR
Mass Spectrometry
Lead
Optimization
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In Vitro
Studies
Comp. Chemistry **
• Biological Eval.
Medicinal Chemistry**
• Flow Cytometry*
Crystal & X-ray
• Imaging*
NMR
Mass Spectrometry
Biophysical Analysis*
Structural Biology
Blue = CCSG Supported Shared Resource
Black = Bindley Biosciences Center Supported Shared Resource
* = Indiana CTSI Designated Core **In process
In Vivo &
Preclinical
Studies
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Biological Eval.
Transgenic Mouse*
Imaging*
Flow Cytometry*
Trans. Pharmacol.*
Biomolecular Screening and Drug Discovery Core Facility
Bindley Biosciences Center
We can currently screen up to 15K to
25K compounds per 8 Hour Day!
Larisa Avramova
lva@purdue.edu
Shilpa Parakh
sparakh@purdue.edu
• 96-well, 384-well and 1536-well
format
• Biochemical and Cellular Assays
• Automated liquid-handling
Robotics – 3 Biomek FX Systems
and others, QPix
• VP Scientific 384-Well Pin Tools
• Multi-Mode Plate Readers
• High-throughput cloning and
protein expression, purification
• Chemical and biologic screening
• HT PCR and kinetic PCR
• Multiplex genetic analyzer –
Beckman GeXP
Purdue Compound Libraries (~220K)
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ChemBridge DiverSet (30,000)
ChemBridge CNS Set (20,000)
ChemBridge NovaCore (50,000)
Asinex Lead/Drug Like (60,000)
LifeChemicals Cherry Picked (30,000)
ChemBridge-Cherry Picked (25,000)
ASDI Lead/Drug Like (6,800)
ChemDiv Fragment (2,000)
LOPAC1280 Pharma Active (1,280)
Collaboration compounds (>1,000)
Natural product library (~1,500)
Format
96-well and 384-well at 10 mM in DMSO
Delivery with Pin Tools 200 nL or 6 nL
Drug Discovery and Development at Purdue
Filling in ‘Chemical Space’
Compound Library Design & Sharing with Notre Dame and IU
Chemical Space Coverage of Purdue and IU Compound Libraries. 3D Principle-component
analysis of Drug-Like Properties. Only the portions of the library closest in chemical space to
the compounds in the LOPAC® library are shown.
Computational and Medicinal Chemistry
Shared Resource
DrugDiscovery.Purdue.edu
Dr. Sergey Savinov
College of Science-IT and Purdue ITaP
Provide Database and Server Maintenance
Computational and Medicinal Chemistry
Shared Resource
Cheminformatics and Structure-Based Design component was Established in 2012 via
funding from Center for Cancer Research, Walther Cancer Foundation (Mesecar Grant)
Discovery Park and Indiana CTSI
Basic Services Included with HTS in Biomolecular Screening Facility in Bindley
 Compound Database –Web-based Oracle database using Dotmatics suite of
programs (Browser)
 Cheminformatics Analysis (Compound Cluster & Substructure Analysis) –Extensive
Analysis Suite of Programs via Dotmatics software platform (Browser, Vortex,
Gateway, Studies, Notebook, Nucleus, Pinpoint) or Canvas in the Schrödinger
Small Molecular Suite of Programs
Enhanced Services that can be used in Conjunction with HTS
 Protein Structural Analysis & Homology Modeling
 In silico screening – Against our in-house 220K compound library, Zinc database
etc. Can provide enrichment factor for choosing libraries and individual plates to
test. Schrödinger Small Molecular Suite of Programs
 Computational Docking – Flexible ligands and Flexible Receptor capabilities.
 Other - 2D/3D QSAR, Core Hopping, Predictive ADMET
Computational and Medicinal Chemistry
Shared Resource
Medicinal Chemistry Core Component was Established October 21st, 2013 with
support from the Walther Cancer Foundation.
Support of HTS, hit-2-lead follow-up (SAR) and scale-up for animal studies.
Long-term, this shared resource will expand to include non-cancer related projects
to support Purdue and CTSI faculty as a campus and CTSI resource.
Formally at Frederick National Laboratory for Cancer
Research - National Institutes of Health
Post-Doctorate Research with Professor Gunda Georg
Department of Medicinal Chemistry, Univ. Minnesota
Graduate Work with Prof. Iwao Ojima
Chemistry Department, SUNY Stony Brook
Antonella Pepe, PhD
Lead Optimization – Macromolecular Crystallography Shared Resource
Dr. Nic Steussy (PCCR) & Dr. Dinesh Yernool (Bindley Biosciences)
High-Throughput Crystallization, Crystal Imaging and Crystal Optimization
LS-CAT
LRL-CAT
High-Throughput X-ray Data Collection
Drug Discovery and Development at Purdue
Accelerating New Collaborations and Navigating Through
Shared Resources for Drug Discovery
Target
Discovery &
Selection
iCTSI or
Center Programs
• CIS
• CSB
• MC
• DDMS
Hit-2-Lead
Discovery
Scientists
Dr. Larisa Avramova
Shilpa Parakh
Dr. Sergey Savinov
Lead
Optimization
In Vitro
Studies
Scientists
Dr. Sergey Savinov
Dr. Antonella Pepe
Dinesh Yernool
Scientists
Dr. Ben Elzey-2D
Cell Culture
Dr. Sophie
Lelievre – 3D Cell
Culture
In Vivo &
Preclinical
Studies
Scientists
Dr. Ben Elzey - MDE
Dr. Aaron Taylor-Imaging
Dr. Greg Knipp – PK
Dr. Steve Byrn - Formuation
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