Center Capabilities
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 |
| Sanford 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 | Alison Neal | 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 | Lucile White | 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 |
Broad Chemistry Capabilities
| Synthesis Formats | Synthesis Capabilities | Analysis, Purification, and Compound Management Capabilities | Chemoinformatics Capabilities | Center Drive Project Capabilities | Biological/Med Chem Expertise |
|---|---|---|---|---|---|
| Solution-phase | Serial | High-throughput analytical-scale RP HPLC with photodiode array UV, ELSD, CAD; SFC for chiral separations | Virtual compound library enumberation and screening | Target ID using SILAC | 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 and toxicology | Anti-infectives | |
| Solid-phase synthesis using Lanterns with Radio-frequency ID tags | Combinatorial | Automated medium pressure liquid chromatography (ISCOs) for silica chromatography | Hit clustering and data mining | Cancer | |
| Mircrowave | Medium-throughput, automated, 5 mm tube-based 1H and 13C NMR | 1D/2D/3D modeling | Cell permeation | ||
| State-of-art compound management capabilities including acoustic preprinting of assay ready plates, individual tube retrival for dry powders and solutions | Central nervous system | ||||
| In vitro ADME (Aqueous Solubility, Plasma Stability, Plasma Protein Binding) | Diversity Oriented Synthesis |
Sanford 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 |
Sanford-Burnham Chemistry Capabilities
| Synthesis Formats | Synthesis Capabilities | Analysis, Purification, and Compound Management Capabilities | Chemoinformatics Capabilities | Center Driven Project Capabilities | Biological/Med Chem Expertise |
|---|---|---|---|---|---|
| Solution-phase | Serial and Parallel | High-throughput analytical/preparative-scale RP HPLC/photodiode array UV/HRMS | Hit clustering and most common structure identification | AS-MS screening | Analog design |
| Solution-phase using solid-phase reagents or scavengers | Serial and Parallel | Mass-directed preparative-scale RP HPLC/dual-wavelength UV/LRMS/ELSD | HTS data analysis and data mining | Fragment-based screening | Cancer, CNS, Immunology, Nuclear Hormone |
| Solid-phase | Combinatorial | Automated NMR (400, 500, 600, 700, 800 MHz) | Analog-by-Catalog SAR and cheminformatics scaffold hopping | Fragment-based drug optimization | GPCRs- mGluRs, chemokine receptors, CNS, Antigen |
| Microfluidic continuous flow | Microwave | In Vitro ADME/T (CYPs, Protein binding, microsome and hepatocyte stability (across species), metabolite ID, functional hERG) | Virtual library screening by structure similarity searching, in silico docking and pharnacophore modeling | Allosteric modulation | |
| Large Scale Synthesis (>10g) | Chiral | In vivo Compound Exposure Studies (rat/mouse PK, Brain/plasma) | Structure-Based drug design | Synthetic Methodology | |
| Continuous flow | Physicochemical measurement: solubility, logD, logP, reactive functionality | In silico property prediction, including ADME, toxicology, and metabolic profiling | Phenotypic High Content visualization | ||
| Protein homology modeling | Natural Products | ||||
| QSAR modeling | |||||
| HTS library design and focused library design | |||||
| Compound and compound library registration, inventory management |
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 |
NCGC Chemistry Capabilities
| Synthesis Formats | Synthesis Capabilities | Analysis, Purification, and Compound Management Capabilities | Chemoinformatics Capabilities | Biological/MedChem Expertise |
|---|---|---|---|---|
| Solution-phase | Serial | High-throughput analytical/prepative-scale RP HPLC/dual-wavelength UV/LRMS/ELSD | Various docking methods; QSAR, CoMFA | Analog design and SAR studies |
| Solution-phase utilizing solid-phase reagents and/or scavengers | Parallel | Agilent-TOF/HRMS (exact mass determination) | Pharmacophore perception and docking | Target identification using activity-based probe molecules (biotin or Click chemistry) |
| Solid-phase | Combinatorial | 2 Automated NMRs (400 MHz) | Virtual compound library enumeration and screening | Natural Product Synthesis |
| Large Scale Synthesis (10 to ~100 g) | Microwave | 3-walkup access Aglient LC/MS/dual-wavelength UV/ELSD | In silico property calculation, including ADME, toxicology, and metabolic profiling | Synthetic methodology |
| Stereoselective | Analytical (methods development) and preparative Chiral HPLC | Compound clustering, HTS data mining | All therapeutic areas including rare and neglected diseases | |
| Air-sensitive (glove box) | Automated sample handling (bar coded vials/matrix tubes) Sirius robot for liquid handling | Shape-based clustering; Isostere replacements | All Biochemical and Cell-Based Systems; Phenotypic High Content Imaging |
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 |
Scripps Chemistry Capabilities
| Synthesis Formats | Synthesis Capabilities | Analysis Purification and Compound Management Capabilities | Chemo-informatics (Cheminformatics) Capabilities | Biological & MedChem Expertise |
|---|---|---|---|---|
| Solution phase (mg to multi-gram scales) | Serial | Automated 400 MHz NMR | Hit clustering and data mining | Enantioselective methods |
| Parallel solution synthesis | Parallel | LC-MS | Structure based inhibitor design; homology model construction | Analog design and SAR studies |
| Solid Phase | Combinatorial | HPLC (reverse and normal phase) parallel chromatography | Virtual compound library screening | Synthetic methodology |
| Enantioselective | Column Enantioslective Analysical methods chromatography | In silico property calculations | Enzyme modulators: Transferases (including kinases), Hydrolases (including cysteine, aspartyl and metalloproteinases), Oxidoreductases, Lyases, Isomerases, Ligases | |
| Organometallic | Compound solubility | GPCR ligands (orthosteric and allosteric) | ||
| Inert atmosphere | Glutathione stability | Nuclear receptor modulators | ||
| Microwave | In vitro DMPK (CYPs,microsome stability--human, mouse and rat;protein binding;metabolite ID) | Transporters | ||
| In vivo DMPK (mouse/rat PK;brain-plasma ratios;tissue distribution) | Ion Channel Modulators | |||
| Fully automated sample registration, storage & distribution | Cancer/Oncology targets | |||
| Anti-Infectives | ||||
| Protein-protein interactions | ||||
| Central Nervous System Targets | ||||
| Natural Product Chemistry | ||||
| Natural Product total synthesis | ||||
| Natural Product scale up |
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) |
