MLPCN Probe Production Centers
The Production Phase of Molecular Libraries Program began on Sept 2, 2008.
Nine Centers Comprise the Molecular Libraries Probe Production Centers Network
Center Name | Center Information | Center PI | Center Contact | NIH Contact |
---|---|---|---|---|
Broad Institute Comprehensive Screening Center | Center Website Center Abstract Capabilities | Stuart Schreiber | Robert Gould | Carson Loomis |
Burnham Center for Chemical Genomics | Center Website Center Abstract Capabilities | John Reed | Thomas Chung | Carson Loomis |
NIH Chemical Genomics Center | Center Website 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 | Colleen Jonsson | 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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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) |