Science for Life Drug Discovery Resources at Purdue Andrew Mesecar, PhD Deputy Director, Purdue Center for Cancer Research Walther Professor of Cancer.
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Science for Life
Drug Discovery Resources at Purdue
Andrew Mesecar, PhDDeputy Director, Purdue Center for Cancer ResearchWalther Professor of Cancer Structural BiologyDepartment of Biological Sciences and Department of Chemistry
iCTSI - Molecular Therapeutics & Drug Discovery – April 21st, 2014
• Biomol. Screening**• Comp. Chemistry• Medicinal Chemistry• NMR• Mass Spectrometry
• DNA Sequencing• Proteomics*• Metabolite Profiling*• Transgenic Mouse* • BioInformatics
• Comp. Chemistry **• Medicinal Chemistry**• Crystal & X-ray• NMR• Mass Spectrometry• Biophysical Analysis*• Structural Biology
• Biological Eval.• Transgenic Mouse*• Imaging*• Flow Cytometry*• Trans. Pharmacol.*
• Biological Eval.• Flow Cytometry*• Imaging*
Blue = CCSG Supported Shared ResourceBlack = Bindley Biosciences Center Supported Shared Resource* = Indiana CTSI Designated Core **In process
Center for Cancer Research and Bindley Biosciences CenterIntegrating Shared Resources into Drug Discovery at Purdue
Biomolecular Screening and Drug Discovery Core FacilityBindley Biosciences Center
We can currently screen up to 15K to 25K compounds per 8 Hour Day!
• 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 GeXPLarisa Avramovalva@purdue.edu
Shilpa Parakh
sparakh@purdue.edu
Drug Discovery and Development at Purdue
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)
Format96-well and 384-well at 10 mM in DMSODelivery with Pin Tools 200 nL or 6 nL
Purdue Compound Libraries (~220K)
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.
DrugDiscovery.Purdue.edu
Dr. Sergey Savinov
College of Science-IT and Purdue ITaP Provide Database and Server Maintenance
Computational and Medicinal Chemistry Shared Resource
Computational and Medicinal Chemistry Shared Resource
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
Basic Services Included with HTS in Biomolecular Screening Facility in Bindley
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
Antonella Pepe, PhD
Post-Doctorate Research with Professor Gunda GeorgDepartment of Medicinal Chemistry, Univ. Minnesota
Graduate Work with Prof. Iwao OjimaChemistry Department, SUNY Stony Brook
Formally at Frederick National Laboratory for Cancer Research - National Institutes of Health
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.
Computational and Medicinal Chemistry Shared Resource
Drug Discovery and Development at Purdue
High-Throughput Crystallization, Crystal Imaging and Crystal Optimization
Lead Optimization – Macromolecular Crystallography Shared ResourceDr. Nic Steussy (PCCR) & Dr. Dinesh Yernool (Bindley Biosciences)
LS-CAT
High-Throughput X-ray Data Collection
LRL-CAT
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Accelerating New Collaborations and Navigating Through Shared Resources for Drug Discovery
ScientistsDr. Larisa AvramovaShilpa ParakhDr. Sergey Savinov
ScientistsDr. Sergey SavinovDr. Antonella PepeDinesh Yernool
ScientistsDr. Ben Elzey-2D Cell CultureDr. Sophie Lelievre – 3D Cell Culture
ScientistsDr. Ben Elzey - MDEDr. Aaron Taylor-ImagingDr. Greg Knipp – PKDr. Steve Byrn - Formuation
iCTSI or Center Programs•CIS•CSB•MC•DDMS
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