ABSTRACT

In a typical drug discovery program, HTS laboratory activities are usually one of many components that make up the overall process from target identi cation to hit con rmation. For illustrative purposes, we present the Emory University Molecular Library Screening Center (MLSC) process ow (Figure 11.1), in which HTS activities are placed in relation to the overall center approach to drug discovery. Not all the elements shown in Figure 11.1 will be present in other academic laboratories, let alone pharmaceutical/biopharmaceutical companies. But the central themes of assay development, namely compound libraries, HTS, structure optimization, and secondary bioassay, are most likely common. Because such centers are state or federally funded, the owchart begins with securing funding and ends with uploading data to PubChem (http://pubchem.ncbi.nih.gov/), a free database of chemical structures of small organic molecules and information on their biological activity. The HTS laboratory is highlighted at the center of the overall process ow. Inspired by the NIH Roadmap Molecular Libraries and Imaging Program, academic institutions worldwide have established centers to facilitate the discovery of small molecules that might eventually be developed into therapeutics. Emory University is one of many such institutions that have established HTS core facilities. A list compiled by the Society for Biomolecular Sciences can be found at http://web.memberclicks.com/mc/ directory/viewallmembers.do. When last accessed (January 2009), the directory comprised 57 screening centers. Most centers list types of libraries (e.g., small molecules) and size (number of compounds in the library), therapeutic or target focus, as well as readout (transduction) technologies available at the facility.