High-Throughput Screening (La Jolla)


The High-Throughput Screening (HTS) facility is a part of Conrad Prebys Center for Chemical Genomics and has the necessary infrastructure to conduct chemical libraries screenings of biological targets. It provides diverse screening instrumentation, compound libraries and expertise on high throughput screens and automation in support of collaborative, and user- or facility-driven screening projects. HTS works closely with Assay Development and High-Content Screening teams to help select and implement the most suitable biochemical or cellular assays for each project, including diverse plate-reader and imaging assays.

The Prebys Center has existing collaborations with a limited number of pharma and biotech organizations, along with several clinical hospitals, to develop small molecule therapeutics. We continue to seek potential additional partnerships of mutual benefit. These partnerships typically involve a portfolio of projects the Prebys Center drives (in collaboration with the partner) through the early stages of the drug discovery process (assay development thru lead optimization to in vivo POC). Often we engage in a pilot project with the partner, which then evolves into a broader collaboration/”shared pipeline." We are not currently engaging in fee-for-service activities.


  • Consultation on high throughput screening approaches
  • Conversion of cell-based and biochemical assays to high-throughput/automation compatible formats
  • Preparation and handling of compound libraries for high throughput screening
  • Screening small-molecule compound libraries in 384- or 1536-well formats with various detection technologies (absorbance, fluorescence, luminescence, fluorescence polarization (FP), TR-FRET, AlphaScreen)
  • Screening data analysis and support for HTS hit follow-up studies
  • Help with the use of automated instrumentation

Equipment and Resources

  • The High-throughput screening (HTS) system (HighRes Biosolutions) is a fully integrated automated screening system equipped with a Staubli TX90XL robotic arm, a 420-plate random-access carousel for storage of compound and assay plates, a 210-plate STX240 Liconic incubator for cell-based assays, two Velocity 11 VSpin centrifuges, a Perkin Elmer ViewLux multimode CCD based uHTS plate reader, a Pherastar FS plate reader, a Labcyte Echo 555 Acoustic Liquid Handler, a Nexus XPeel and Agilent PlateLoc for re-sealing plates, a BioTek EL406 plate washer, a high-speed 10-position HighRes pintool device with ultrasonic baths and four multidrop Combi dispensers. It enables fully automated large-scale screening of biological assays with various formats.
  • Access™ Laboratory Workstation (Labcyte) is an automated compound-dispensing system including an Echo 555 Acoustic Liquid Handler, a precise automation robotic arm, four random-access 20-plate racks, a de-lid station, a Deerak GX Series low-volume bulk dispenser, a Agilent V-Spin centrifuge, a Nexus XPeel and a Agilent PlateLoc and controlled by Labcyte TEMPO automation control software. This system allows fully-automated multiplate small-volume dispense operations especially useful for dose-response tests of large number of compounds, e.g. cherry-pick confirmation of primary HTS hits.
  • Plate processing workstation (Agilent) – The workstation includes a PlateLoc sealer, Vcode barcode labeler, BenchCell 4x with four stackers and a Bravo liquid handler.
  • Stand-alone Instruments
  • Biomek FX liquid handling systems with 96- and 384-well plate heads and Span8 arms
  • PerkinElmer Envision plate readers with 2 reagent injectors
  • Kalypsys washer/dispenser system for rapid and precise dispensing and plate washing in 96, 384, 1536 formats
  • Hamamatsu FDSS7000 rapid-kinetics fluorescence and luminescence plate reader with integrated 384-well liquid handling
  • Labcyte Echo 555 Acoustic Liquid Handler
  • BMG PherastarPlus plate reader
  • Titertek Map-C plate washer
  • BioTek plate washers (EL405, EL406)
  • Molecular Devices M5 plate readers
  • Multiple liquid bulk dispensers (Wellmate, Multidrop Combi)

Compound Libraries

The libraries below are available for collaborative projects performed at CPCCG.

  • Spectrum Collection: A collection of 2,000 compounds of known drugs, reported bioactives and natural products from Microsource Discovery Systems.
  • LOPAC Collection: A collection of 1,280 pharmacologically active compounds from Sigma-Aldrich. This library contains effector molecules for all major target classes.
  • Kinase Inhibitor Collection: A collection of 244 known kinase inhibitors compiled from InhibitorSelect 96-well plates Libraries I, II and III from EMD Biosciences.
  • US and International Drug Collections: Contain 1,040 drugs that have reached clinical trial stages in the USA and 240 drugs that are marketed in Europe and/or Asia but have not been introduced in the US, sold by Microsource Discovery Systems.
  • Greenpharm Natural Product Collection: A collection of 240 known phytochemicals chosen for molecular diversity and drug-like criteria. This library contains 55% of alkaloids, 20% of terpenoids, as well as various flavonoids, coumarins and other phytochemicals, sold by Prestwick Chemicals.
  • Prestwick Chemical Library: The Prestwick Chemical Library® contains 1,200 small molecules, 100% being marketed drugs. The active compounds were selected for their high chemical and pharmacological diversity as well as for their known bioavailability and safety in humans.
  • StemSelect Collection: 303 pharmacologically active, structurally diverse modulators of cell fate from EMD Biosciences. It includes inducers, activators, and agonists for various developmental processes.
  • Bioactive Lipid Library: 201 bioactive lipids from ENZO Life Sciences.
  • Natural Product Library: 502 compounds from ENZO Life Sciences, including compounds from the following classes of products: terpenoids, peptolides, flavones, coumarins, alkaloids, macrolides, soflavones, synthetic derivates.
  • REDOX Library: 80 compounds with defined prooxidant or antioxidant activity from ENZO Life Sciences. A variety of structurally and mechanistically different compound classes are included such as hydroperoxides, polyphenolics, metal chelators, thiols, thiol traps, radical scavengers, lazaroids and glutathione modulators as well as small molecule enzyme mimetics for SOD and glutathione peroxidase.
  • InhibitorSelect Signal Pathway Collection: 64 compounds from EMD Biosciences target several signal pathways (WNT, MAP kinase, EGFR, VEGF, JAK/STAT, NF-rB, AKT/PI3/mTOR).
  • MLSMR Library: Contains approximately 360,000 compounds. It was originally compiled for MLPCN, a NIH Roadmap Inhibitive. The collection includes compound from commercial vendors, research labs around the world, and MLPCN centers. More than 95% compounds in the MLSMR collection are characterized with molecular weight ≤500Da.
  • Sanford-Burnham HTS Library: A large library of approximately 320,000 compounds selected from a pool of over three million compounds from five chemical vendors, ChemBridge, Asinex, Enamine, Life Chemicals, and ChemDiv. They were selected for general HTS screening purpose from a pool of over three million compounds using cheminformatics selection strategies such as a cluster-based 2D-fingerprint approach to ensure diversity balanced with good representation (three to 25 representatives per cluster) and good physicochemical properties (e.g. Lipiski rule of five). Appropriate filters were also applied to exclude compounds with unwanted and reactive groups.
  • Other specialty collections (both commercial and non-commercial sources) of discrete small molecules and natural products.

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