The Production Phase of Molecular Libraries Program began on Sept 2, 2008.

Center Name	Center Information	Center PI	Center Contact	NIH Contact
Broad Institute Comprehensive Screening Center	Center Website Center Abstract Capabilities	Stuart Schreiber	Patti Aha	Carson Loomis
Burnham Center for Chemical Genomics	Center Website Center Abstract Capabilities	John Reed	Thomas Chung	Carson Loomis
NIH Chemical Genomics Center	Center Website Center Abstract Capabilities	Chris Austin	James Inglese	Ingrid Li
The Scripps Research Institute Molecular Screening Center	Center Website Center Abstract Capabilities	Hugh Rosen	Steven Brown / Peter Hodder	Ingrid Li
Johns Hopkins Ion Channel Center	Center Website Center Abstract Capabilities	Min Li	Kelly Campbell	Ingrid Li
University of New Mexico Center for Molecular Discovery	Center Website Center Abstract Capabilities	Larry Sklar	Virginia Salas	Ingrid Li
Southern Research Specialized Biocontainment Screening Center	Center Website Center Abstract Capabilities	Colleen Jonsson	Nichole Tower	Carson Loomis
Kansas Specialized Chemistry Center	Center Website Center Abstract Capabilities	Jeffrey Aube	Cady Bush	Carson Loomis
Vanderbilt Specialized Chemistry Center for Accelerated Probe Development	Center Website Center Abstract Capabilities	Craig Lindsley	Julie Le Engers	Ingrid Li

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Broad Institute Comprehensive Screening Center Capabilities

Assay Formats	Screening Capabilities	Biologicial Expertise
Absorbance	Biochemical Assay Screening - enzyme activity	Cancer Pathways
AlphaScreen	Biochemical Assay Screening - protein:macromolecule (protein/DNA/RNA) binding	Diabetes and Metabolic Disease
Fluorescence Intensity	Biochemical Assay Screening - protein:small molecule binding	Infectious Disease
Fluorescence Polarization	Cell-Based Assay Screening - engineered cell lines (BL1, BL2, BL2+)	Psychiatric Disease
Time Resolved Fluorescence	Cell-Based Assay Screening - primary cells (BL1, BL2, BL2+)	Epigenetic/Chromatin Biology
FRET	Cell-Based Assay Screening - co-cultured cells (BL1, BL2, BL2+)	Regenerative Medicine/Stem cells
TR-FRET	Image-based High-Content Screening	Cell Differentiation (phenotypic assays)
Luminescence	Image Analysis (standard); Image Analysis Algorithm Development (custom)	Cell proliferation and cell death
Automated microscopy (fluorescence, transmitted light)		Cellular signaling pathways
Small molecule microarray		Cytotoxicity Assays
		Enzyme Assays (proteases, kinases, histone deacetylases, histone methylases etc.)
		GFP-based Assays
		Nucleic Acid-based Targets
		Protein Translocation Assays
		Protein-protein Interactions
		Protein-nucleic acid Interactions
		Reporter Assays

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Burnham Center for Chemical Genomics Capabilities

Assay Formats	Screening Capabilities	Biologicial Expertise	Additional Capabilities
Absorbance	Biochemical Assay Screening	Cell Death (Apoptosis, Necrosis etc.)	Structural Biophysical Studies for Protein folding & Ligand Binding Identification of molecular contacts and dyanmics
Luminescence	Cell-Based Assay Screening	Cell Differentiation (phenotypic assays for stem cells using fluorescent reporters)	Full medicinal and synthetic chemistry for SAR develompent, probe optimization
Fluorescence Intensity	High-Content Cell-Based Assay Screening	Cell Proliferation	Including: microwave- and microfluidics assisted chemistries and instrumentation
Fluorescence Polarization	Cell Image Analysis	Cell Motility and Invasion	"Click" Chemistry and photoaffinity probe label design and synthesis
Time Resolved Fluorescence	Image Algorithm Development	Cell Morphology	Analytical Chemistry for structure elucidation and compound QC by NMR & LC-MS with full PDA traces from 190 - 400 nm
FRET	Cell Reporter Assays	Cell Pathway Assay for pathway deconvolution of phenotypic assays	Small molecule compound scale up (10-50 mg) and purification
TR-FRET	NMR-based Ligand Optimization	Cytotoxicity Assays	Exploratory pharmacology with rapid in vitro ADMET/PK profilingwith surrogate assays
Heterogeneous Assay Formats (ex: ELISA)	Virtual Library Design/Screening	Enzyme Assays	Rapid limited dose in vivo mouse/rat studies for ADMET/PK profiling: RACE
NMR	In Silico Profiling	Kinase Assays
	Computer Aided Drug Discovery/Structure Based Drug Design	Phosphatase Assays
	Micro-Isothermal Calorimetry validation of compound binding to target	Thioesterases
	1D & 2D NMR validation of compound binding to target	Glycosylation enzymes
		Protease Assays
		ER Stress/Chemical Chaperone Assays
		Protein Translocation Assays
		Protein-protein Interaction Assays
		Cardiac myocyte Assays
		Pancreatic beta-cell Assays
		Neuroregeneration Assays
		Promoter/Reporter Assays
		Actins, Microtubulus and Microfilament Structures
		Cancer
		Diabetes
		Inflammation and Infectious Diseases
		Nucleic Acid-based Targets
		Functional Genomics/cDNA/siRNA Profiling
		PK/ADME/Toxicity Profiling:microsomal stability, PAMPA, plasma protein binding, solubitlity, stability
		Protein Expression
		Tissue culture scale up
		Selectifivity Profiling
		CYP450 Profiling Assays

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NIH Chemical Genomics Center Capabilities

Assay Formats	Screening Capabilities	Biologicial Expertise
Absorbance	1536 well plates; HTS (Primary) and secondary screens	Enzyme assays (kinase, phosphatase, protease, etc.)
AlphaScreen	1536 well plates; HTS (Primary) and secondary screens	Protein-protein interaction, replacement of ELISA assay, protein-peptide interaction
Fluorescence Intensity	1536 well plates; HTS (Primary) and secondary screens	Enzyme assays (kinase, phosphatase, protease, beta-lactamase reporter, etc.); Receptor binding assay
Fluorescence Polarization	1536 well plates; HTS (Primary) and secondary screens	Protein-peptide interaction, protein-DNA/RNA interaction, Kinase assay (IMAP)
Time Resolved Fluorescence	1536 well plates; HTS (Primary) and secondary screens	Redox enzyme systems
HTRF/LANCE (FRET)	1536 well plates; HTS (Primary) and secondary screens	cAMP assay, Kinase assay
Luminescence	1536 well plates; HTS (Primary) and secondary screens	Enzyme assays, luciferase reporter-gene assay, cytotoxicity/cell growth assay (ATP content)
Laser scanning cytometry (Acumen Explorer)	1536 well plates; HTS (Primary) and secondary screens	GFP assay, nuclear translocation assay
Microscopy-based imaging (INCell 1000)	1536 well plates; secondary screen	GFP-based assays, antibody/dye staining assays
FDSS-7000 Kinetic Reader	1536 well plates; HTS (Primary) and secondary screens	Intracellular calcium kinetic assay (GPCRs and Calicum channels), ion flex assay (Ion Channels), aequorin assay (GPCRs)
Real-time cell analyzer (Acea’s impedance-based platform)	16 well strip/96 well plate; secondary kinetic assay	Cell growth rate, cytotoxicity kinetic measurement
		BLS-2 level assays for infectious diseases

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The Comprehensive Center for Chemical Probe Discovery and Optimization at Scripps Capabilities

Assay Formats	Screening Capabilities	Biologicial Expertise
Fluorescence Intensity	Cell Imaging	GPCRs
Fluorescence Polarization	Fluorescent Microscopy	Receptor-ligand interaction
TRF		Protein-protein interactions
FRET		Enzyme Assays
Luminescence		Ion Channels
Absorbance		Reporter Assays
AlphaScreen		Viability Assays
FITC		Protein Translocation
GFP

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Johns Hopkins Ion Channel Center Capabilities

Hopkins Capabilities

Assay Formats	Screening Capabilities	Biologicial Expertise
Absorbance	Biochemical Assay Screening	Ion Channels
Fluorescence Intensity	Cell-Based Assay Screening	Yeast two-hybrid screening
Time-resolved Fluorescence	High-Content Cell-Based Assay Screening	Protein-protein interactions
Fluorescence Polarization	Ikr profiling	Enzyme Assays
FRET		Reporter Assays
TR-FRET		Receptor-ligand interaction
High-throughput kinetic fluorescence reader (FDSS)		Protein Translocation
Luminescence		GPCRs
Automated microscopy (fluorescence, transmitted light)		Viability Assays
High throughput label-free Biochemcial and cell-based detection (Epic system)
Ion Channel Readers, atomic absorption spectroscopy-based
Automatic patch-clamp

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University of New Mexico Center for Molecular Discovery Capabilities

UNM Capabilities

Assay Formats	Screening Capabilities	Biologicial Expertise
High-throughput flow cytometry (384-format; 1536 in development)	Real-time kinetic analysis of cell responses and assemblies	Protein-protein, protein-small molecule and protein -nucleic acid interactions
Steady-state and lifetime, real-time kinetics of homogeneous solutions	Cell-based assays: labeling, immunophenotyping, complex cell mixtures, cellular functional assays	Microbiology
Fluorescence and phase-contrast microscopy	Bead-based Assays: analytes and assemblies	Receptors
Plate-based fluorescence, absorbance, polarization, and luminescence	Informatics (virtual screening and in silico profiling)	Transporters
Profiling (Luminex platform)	Multiparametric detection for high content analysis	GPCRs
	Multiplex analysis format: primary HTS assay selectivity screening and dose-response screens for compound profiling of target families	Kinase biology
	High-throughput analysis of compound solubility	Yeast biology: yeast - molecular assemblies; GFP strain collections, yeast hybrid analysis, display libraries; cell cycle/ DNA content analysis
	High-throughput and multiparametric analysis of compound fluorescence (3 colors of excitation, 9 colors of emission)	Conversion of molecular assays to flow-cytometry-based multiplex (e.g.from TR-FRET, alpha screen or polarization formats)
	Homogeneous (no wash assays) resolution of free and bound fluorescence for ligand binding/protein assemblies to 500 nM	Integrins and adhesion molecule biology
		Proteasome biology

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Southern Research Specialized Biocontainment Screening Center Capabilities

Assay Formats	Screening Capabilities	Biologicial Expertise
Fluorescence Intensity	Cell-based Assays	BSL2 and 3 HTS containment and processes for viruses and bacteria
AlphaScreen	Biochemical Assays	Viability Assays
Time-resolved Fluorescence (TR-FRET)	Fluorescent Microscopy	Reporter Assays
Absorbance		Enzyme Assays
Luminescence		ELISA Assays
GFP, YFP, RFP
FITC

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Kansas Specialized Chemistry Center Capabilities

Synthesis Formats	Synthesis Capabilities	Analysis, Purification, and Compound Management Capabilities	Chemoinformatics Capabilities	Center Driven Project Capabilities	Biological/Med Chem Expertise
Solution-phase	Serial	High-throughput analytical-scale RP HPLC/photodiode array UV/HRMS	Virtual compound library enumeration and screening	Target identification and localization using affinity labeling of probe compounds	Analog design
Solution-phase using solid-phase reagents or scavengers	Parallel	High-throughput mass-directed preparative-scale RP HPLC/dual-wavelength UV/LRMS/ELSD	In silico property calculation, including ADME, toxicology, and metabolic profiling	Yeast three-hybrid systems as tools for identification of protein targets of probe compounds	Anti-infectives
Solid-phase	Combinatorial	Medium-throughput, automated, 5 mm tube-based 1H and 13C NMR	Pharmacophore perception and docking		Cancer
	Microwave	Compound formatting available in a variety of formats (vials, plates) and solvents	Hit clustering and data mining		Cell permeation
			1D/2D/3D QSAR including COMFA, COMBINE		Central nervous system
					Natural products chemistry
					Nuclear receptor system
					Opioid
					Proteases

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Vanderbilt Specialized Chemistry Center for Accelerated Probe Development Capabilities

Synthesis Formats	Synthesis Capabilities	Analysis, Purification, and Compound Management Capabilities	Chemoinformatics Capabilities	Biological/Med Chem Expertise
Solution-phase	Serial	High-throughput analytical/preparative-scale RP HPLC/photodiode array UV/HRMS	Virtual compound library enumeration and screening	Analog design
Solution-phase using solid-phase reagents or scavengers	Parallel	High-throughput mass-directed preparative-scale RP HPLC/dual-wavelength UV/LRMS/ELSD	In silico property calculation, including ADME, toxicology, and metabolic profiling	Central nervous system (GPCR, Ion Channel, Transporters)
Solid-phase	Combinatorial	Automated NMR (600 MHz)	Pharmacophore perception and docking	Oncology Antiviral Metabolic diseases
Large Scale Synthesis (>10g)	Microwave	Automated sample handling (bar-coded vials) Zinsser Robot for liquid handling	Hit clustering and data mining	Allosteric ligand design (PAMs, NAMs and allosteric agonists)
	Chiral	Analytical and preparative Chiral HPLC	1D/2D/3D QSAR including COMFA, COMBINE	Natural products chemistry
	Glove Box (catalyst screening - 96 well format)	Large scale NP and RP Chromatography	Artificial neural network (virtual screening)	Synthetic Methodology
		In Vitro DMPK (CYPs, Protein binding, microsome and hepatocyte stability (across species), metabolite ID, functional hERG)
		In vivo DMPK (rat/mouse PK, Brain/plasma studies)

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