Pooling for Detection of Synergistic Compounds

• Activity Number: 361
• Type: Invited
• Date/Time: Wednesday, August 11, 2004 : 2:00 PM to 3:50 PM
• Sponsor: Section on Physical and Engineering Sciences
• Author(s): Jacqueline M. Hughes-Oliver*+
• Companies: North Carolina State University
• Keywords: antagonism ; blocking ; drug discovery ; group testing ; high-throughput screening ; synergism

Abstract

Drug discovery is a multiphase process that requires identification of chemically distinct classes of lead compounds. Given a particular target or biological assay, lead compounds must demonstrate high potencies. Screening to identify potential leads or active compounds can be both time-consuming and expensive because of the large numbers of compounds available in either real or virtual libraries. Motivated by historical observations that only a small fraction, say 5%, of tested compounds are active to a particular assay, some pharmaceutical companies now use pooling experiments for screening. Pooling experiments, where multiple compounds are tested in a single well, are cost-effective and information-dense. They are also ideal for detecting synergism, where two or more compounds are required to achieve activity. Unfortunately, their analysis can be fraught with difficulties. One such difficulty arises from blocking mechanisms that result in an inactive pool containing active compounds. I will present some methods for analyzing pooling experiments, discuss their successes and failures, and illustrate application to a real dataset.