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A High Throughput Assay for the Repurposing and Development of Drug Compounds as Novel Antibiotics

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A High Throughput Assay for theRepurposing and Development of Drug Compounds as Novel Antibiotics Princeton Docket # 15-3074 The Gitai Laboratory at Princeton University has developed a high throughput assay to screen existing small molecule compound libraries to identify antibiotic activity with novel mechanisms of action. This assay can facilitate the rapid and inexpensive development of the novel use, or repurposing, of these compounds and their derivatives as new antibiotic drugs.  Gitai Lab’s high throughput assay was developed to accommodate practical situations where screening large compound libraries with high resolution of the compound’s mechanisms of action is necessary. Gitai Lab expanded beyond the cytological profiling (BCP) assay originally developed by Nonejuie et al. (PNAS 2013) beyond cytological profiling, and considers molecular (e.g., DNA) profiling and temporal evolutionary features. Machine learning is implemented and a training set of known compounds was used. The throughput of the assay has been improved to accommodate more than 100 samples a day.  As a result, this assay has the resolution and accuracy to have utility in practical screening situations where the compound library is large. To date, this method has been validated on 141 known antibiotics, and has identified 48 new candidate antibacterial compounds. As a proof of concept, SCH79797 was found to exhibit potent bactericidal activity and novel mechanism of action that can be potentially be used for treating cancer. The Gitai Lab is seeking industrial partners in the further development and implementation of this assay.  Applications: - Screening of compound libraries for drug repurposing. - Identification of antibacterial drug where previously unknown. - Identification of novel mechanisms of action that allow for novel use or repurposing. Advantages: - Economical high throughput screen with basic instrumentation. - Rapid, efficient, and cost effective means to drug development. - High resolution and accuracy designed to accommodate large compound libraries. Intellectual Property & Development Status:Patent protection is pending.Gitai lab is currently seeking commercial partners for the further development and commercialization of the high throughput assay. The Inventors: Zemer Gitai is the Edwin Grant Conklin Professor of Biology in Department of Molecular Biology. His research focuses on the cell biology of bacteria.  His lab studies how cells self-organize across spatial scales, using quantitative, molecular, and engineering approaches.  His work discovered new components of the bacterial cytoskeleton, new functions for bacterial polymers in metabolism, compartmentalization, and chromosome dynamics, and established the importance of protein assembly for unexpected processes like metabolism and pathogenesis.  Prof. Gitai's achievements have been recognized by many prestigious awards, including the NIH New Innovator Award, the Beckman Young Investigator Award, and the HFSP Young Investigator Award. James Martin, Hsin-Jung Li, and Max Wilson are postdoctoral candidates in the Gitai lab.  Hahn Kim is the Director of the Small Molecule Screening Center at Princeton University.  Contacts: Linda JanPrinceton University Office of Technology Licensing • (609) 258-3653 • ljan@princeton.edu Laurie TzodikovPrinceton University Office of Technology Licensing • (609) 258-7256 • tzodikov@princeton.edu

*Abstract

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*Principal Investigation

Name: Zemer Gitai, Associate Professor of Molecular Biology

Department: Molecular Biology

Name: Maxwell Wilson, postdoc - Research Assoc.

Department: Molecular Biology

Name: Hahn Kim, Director, Small Molecule Screening Center

Department: Chemistry

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美國