Drug Discovery

Recognizing the importance of small molecules and the growing interest in screening them for basic and translational research, this University of Utah Shared Resource provides a low-cost alternative to the purchase of large, costly libraries for individual labs. The Drug Discovery Core serves to aid in the identification of novel compounds for a wide range of interests at the University of Utah.

The Drug Discovery Core at the University of Utah is an established Service/Recharge center that provides compound collections for screening by University of Utah Faculty. Our mission is to provide customers low-cost and efficient access to chemical libraries for screening, to equipment for automation, and to synthetic chemistry support for the characterization and validation of compounds for potential use as therapeutics, diagnostics and biological tools.

If you would like to make a reservation for use of our equipment or for our services, please go to resource.cores.utah.edu.

We request that all labs publishing work that relies at least partially on work we’ve performed acknowledge our core facility with something along the lines of:

Work was performed by the Drug Discovery Core Facility, a part of the Health Sciences Cores at the University of Utah.

Services We Offer
  • High-throughput screening
  • Small molecule chemical libraries
  • Pooled CRISPR-Cas9 libraries
  • Assay development
  • Consultation on target identification/validation, hit to lead optimization, PK/PD/Efficacy
  • Chemical support for drug discovery
  • Virtual Chemistry screening
  • Synthetic chemistry support
  • Follow-up assays on hits

 

To obtain compounds from the Drug Discovery Core:

  1. Please complete a Work Authorization Form
  2. Fax it to Bai Luo at (801)-585-6364
  3. Email bai.luo@hsc.utah.edu to get a quote and order compounds
LIbraries & Collections

CRISPR Libraries Available for Screening

  1. The genome-scale CRISPR-Cas9 knockout (GeCKO) v2 library consists of 122,417 unique guide sequences targeting 19,052 human genes and including 1000 control (non-targeting) sgRNAs.
  2. Subset CRISPR libraries: a) human Lentiviral sgRNA library-kinases, and b) human Lentiviral sgRNA library-nuclear proteins.

Commercial Compound Libraries Available for Screening

  1. Chembridge DIVERSetTM 100K Libraries:We offer two, complementary DIVERSet™ libraries: The DIVERSet™-EXP library and the DIVERSet™-CL library. Each library offers a diverse set of 50,000 compounds with extensive pharmacophore coverage for primary screening. Stringent druglike and desirable chemical group filters coupled with a 3D conformer analysis are used in selecting a premium set of 50,000 druglike compounds with maximum pharmacophore coverage and chemical diversity.
    http://chembridge.com/datasheets/DIVERSet.pdf
  2. Microsource Spectrum Collection: 2000 compounds with varied of biological activity and structural diversity, including 1000 known drugs from United States, Europe, and Japan.
    http://www.msdiscovery.com/spectrum.html
  3. NIH Clinical Collection: 446 compounds that have been in phase I-III clinical trials and have not been represented in other arrayed collection.
    http://www.nihclinicalcollection.com
  4. Epigenetics Screening Library: 75 small molecules that are known to modulate the activity of a variety of epigenetic ‘writers and erasers’ and ‘reader’ proteins.
  5. NCI Diversity Set IV: 1596 compounds with diverse pharmacophores which were derived from the almost 140,000 compounds available for distribution from the Developmental Therapeutics Program (DTP) repository at NCI/NIH.
    Click here for more information
  6. Natural Products Set II: 120 natural product compounds from Developmental Therapeutics Program (DTP) repository at NCI/NIH.
    Click here for more information
  7. Enamine 3D Diversity Set: 50240 compounds were selected from the drug-like portion of Enamine HTS collection (1.3 million compounds) by application of conformational analysis and shape clustering algorithms. Click here for more information
  8. Protein Kinase Inhibitor Library:  160 well-characterized, cell-permeable, potent, and reversible protein kinase inhibitors; the majority of which are ATP-competitive.
  9. Approved Oncology Drugs Set II: The current set (AODVII) consists of 129 agents and is intended to enable cancer research, drug discovery and combination drug studies.
  10. Natural Products Set IV: The Natural Products Set IV consists of 419 compounds that were selected from the DTP Open Repository collection of 140,000 compounds.
  11. Mechanistic Set III: The Mechanistic Set III, which consists of 813 compounds, was derived from the 37,836 open compounds that have been tested in the NCI human tumor 60 cell line screen. This mechanistic diversity set was chosen to represent a broad range of growth inhibition patterns in the 60 cell line screen, based on the GI50 activity of the compounds.
  12. Details of these three libraries can be found here: https://dtp.cancer.gov/organization/dscb/obtaining/available_plates.htm

*Private Chemical Collections

  1. UUPCC – University of Utah Private Chemical Collection: A library of 120,000 compounds obtained from the former NPS Pharmaceutical Company. Many compounds in this library are unique and not commercially available, creating a valuable resource for the University. Due to the unique nature of this library, access will require a written proposal.
    Click here for more information
  2. Dept of Chemistry Library: A diverse collection (800 compounds) of molecular skeletons that represent the chemical interests of individual principal investigators. These compounds are all prepared by chemical synthesis within their laboratories and generally reflect natural product substructures or analogues of proven pharmacophores.
  3. Ireland Natural Product Collection:A set of natural products (240 compounds) isolated from marine invertebrate animals and micro-organisms. The collection reflects a wide array of natural product scaffolds and biosynthetic pathways. All compounds have been purified by HPLC and chemically characterized.
  4. The CIT Fragment Library: A unique collection of over 1000 molecular fragments created by the Center for Investigational Therapeutics at the Huntsman Cancer Institute. By screening this collection, one can cover larger chemical space and the high structural diversity helps avoid intellectual property conflicts.
  5. Spider Venom Collection: A small library, also obtained from NPS. Available soon.

* These sets of molecules are proprietary and users will be asked to sign an intellectual property advisory notice.

Equipment

Automated Liquid Handling Stations:

  • Tecan EVO100/MCA96 Liquid Handler with sterile bio-hoods
  • Tecan EVO100/MCA384 Liquid Handler with sterile bio-hoods
  • CyBio(Matrix) 96/384 Liquid Handler
  • Matrix PlateMate Plus 384 Liquid Handler
  • HP D300 Digital Dispenser – capable of generating dose response curves which eliminates serial dilution by offering picoliter to microliter non-contact dispensing of small molecules in DMSO directly into assay plate.
    Click here for more information

Automated Detection Systems:

  • ImageXpress XLS Automated High-Content System: capable of providing automated cellular imaging in fluorescent modes for fixed- or live-cell assays
    Click here for more information
  • Bio-tek Plate Synergy 4 Plate Reader with stacker: capable of high-throughput reading of fluorescence, luminescence and absorbance at any wavelengths.
  • Bio-tek Plate Washer with stacker
Pricing

The costs of screening projects can vary greatly depending on the type of screening assay, the compound library, and whether the investigator will have their own people perform the assay or use the Core personnel. Therefore, the Core will work with the investigator to create an individual quote for the project. Below are the rates for hourly use of the equipment and purchase of the individual compound library (1 ul of stock in 96-well format). However, there is additional cost for equipment time, consumables, assay reagents, personnel cost, etc which will vary depending on the final screening.

Library Pricing
Spectrum Library Chembridge Library Kinase Inhibitor Library Chemistry Dept Library Marine Natural Products UUPCC
25 plates for $448.35 613 plates for $10,185.24 2 plates for $271.71 10 plates for $169.80 3 plates for $85.94 Call Bai at (801)-587-1527 for pricing

 

Equipment Usage

User Run: $50/hr
Core Run: $100/hr

Hours of Operation

Monday-Friday 8:30am-5pm

Location

College of Pharmacy, Skaggs Building Room 315

30 South 2000 East

Salt Lake City, UT 84112

Staff

Bai Luo, Ph.D., Director
Phone: 801-587-1527
Fax: 801-585-6364
email: bai.luo@hsc.utah.edu

Oversight Committee

Darrell Davis, Ph.D. (Medicinal Chemistry)
Ryan Looper, Ph.D. (Chemistry)
John Phillips, Ph.D. (Internal Medicine)
Jared Rutter, Ph.D. (Biochemistry)
Hari Vankayalapati, Ph.D. (HCI)