Drug Discovery

Drug discovery is the process by which potential new medicines are identified. Drugs have a positive impact on a disease by binding to target molecules in the body and changing their functions. Discovering novel drug-like molecules starts with either a target-based or phenotype-based approach. In a target-based approach, one theorizes, based on basic research data, that a drug that binds and interferes with the function of a particular protein should help a disease. After a target is identified, then a drug-like molecule is identified that binds to it and alters its function in the desired way. In phenotypic drug discovery, drug-like molecules are discovered that have a positive impact on a disease model system, like the function or health of human cells in culture. 

There are numerous approaches to drug discovery. One method of identifying drug-like small molecules is high-throughput screening (HTS), which is the rapid testing of thousands of diverse, random compounds for ones that have drug-like properties against a target protein or in a disease model system. Thus, HTS requires tests (i.e., assays) to be biologically relevant, rapid, and robust to detect active, drug-like compounds or “hits." HTS assays are formatted into small volumes in high-density microtiter plates (e.g., 384-well plates) where the assays are rapidly and precisely assembled using robotic liquid handling automation and plate-based readers to measure the activity of every compound. Hits from the process of HTS are the starting place whereby the hit is chemically altered, using knowledge gained from iterative rounds of testing and molecule redesigning, to finally identify a drug to be tested in humans.

The High-Throughput Screening (HTS) and Drug Discovery Core Facility is designed to suit assay validation and screening needs. With our flexible screening schedule and shared resources, we can perform the entire screen for you or share our equipment for your screening use. Our facility maintains a large chemical library and houses multiple liquid handling and assay detection instrumentation on site.  Our HTS capabilities extend from 6- to 384-well plates and include almost all detection formats for both biochemical and cellular assays, including absorbance, fluorescence, luminescence, fluorescence polarization, time-resolved fluorescence, FLIPR, high-content imaging, and live-cell detection.

The HTS Core Facility can assist with assay development prior to starting a screen. We optimize assay protocols for automated screening by transitioning from 96 to 384 well formats, miniaturizing and reducing reagent volumes, reducing reagent steps and wash steps.   

We validate assays under optimized conditions to make screening ready by running min and max plates, assessing assay feasibility with Z' scores, and running control compounds in dose response for potency determination and reproducibility