The goal of the Target Validation & Screening (TVS) section is to provide investigators access to automated liquid handling equipment, sensitive high throughput detectors, and diverse collections of screening libraries to facilitate the identification and validation of therapeutic targets as a step towards developing new drugs and therapies. The TVS program provides the expertise in cell-based and in vitro assay development and will assist in adapting an existing assay into higher throughput formats.

Capabilities

Libraries 

Over 200,000 small drug-like compounds in a number of libraries, including:

• Chemical Diversity Labs-- Three non-overlapping diversity libraries (ChemDiv 40K, ChemDiv 55K, ChemDiv 100K) in a 384-well format, each at 10 mM in 100% DMSO.
• Maybridge HitFinder-- Collection of 14,400 drug-like compounds from Maybridge, preselected by the supplier (ThermoFisher), each at 10 mM in 100% DMSO. 
• Maybridge Ro3 Fragment-- Collection of 1,000 fragments, meeting Rule-of-3 compliance, with exceptional diversity and having chemically linkable analogs. Guarantees solubility of the compounds @ 200 mM in DMSO.
• MicroSource Spectrum-- Collection of 2,060 compounds, 50% drugs, 30% natural products, and 20% other bioactive components available in a 96-well format, each at 10 mM in 100% DMSO.
• The Prestwick Collection-- A small library of 1,520 FDA (Federal Drug Administration), EMA (European Medicines Agency), and JAN (Japanese Accepted Name)-approved drugs and is designed with a large chemical and pharmacological diversity.
• NIH Clinical Collection-- Collection of 727 small-molecules that have a history of use in clinical trials. 
• SBi Collection-- Collection of 4,381 compounds collected from several commercial sources plus 67 compounds synthesized in house.

Instrumentation 

• Liquid handling and plate reading instruments
  • Biomek i7, Biomek i5, Biomek FX, and Biomek NxP 
  • BMG CLARIOstar, BMG CLARIOstar Plus, and BMG PHERAStar FS
• Other equipment such as biosafety cabinets, CO₂ incubators, an inverted phase microscope, low speed centrifuges, and dedicated liquid nitrogen storage freezers

Assay Development

• in vitro protein-protein, protein-RNA, and protein-DNA assays 
  • Fluorescence polarization competition assays
  • FRET and TR-FRET
  • AlphaScreens
• Cell-based assays for screening small, drug-like compounds
  • Mammalian cell viability
  • Chemiluminescence gene reporter assays
  • Yeast and bacterial growth
  • Cell-based ELISAs