Extraction, Dereplication, Isolation Chemistry, and Biological Evaluation

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In collaboration with The Ohio State University (OSU; Project 1; Cores B and D), the University of Illinois at Chicago (UIC; Project 2; Core A), and Research Triangle Institute (RTI; Project 3), in Core C Bristol-Myers Squibb (B-MS) plans to identify and evaluate novel anticancer agents derived from various natural product sources (plants, terrestrial cyanobacteria, and filamentous fungi). The Pharmaceutical Research Institute of B-MS is part of one of the largest pharmaceutical companies in the world, with a strong commitment to, dedicated resources for, and a proven track record in natural product drug discovery and development. With respect to this project, we plan to carry out the following Specific Aims: 1. Assay crude and semi-purified extracts as well as isolated pure compounds for cytotoxic and/or cytostatic activity in a diverse tumor cell line panel to aid the discovery of novel anticancer agents. 2. Assay crude and semi-purified extracts as well as isolated pure compounds in various molecular mechanism based/target-driven oncology screens to aid in the identification of novel, targeted anticancer agents. 3. Support activity-guided fractionation of the active constituents either by performing the assays at B-MS or transferring the high throughput screen (HTS) technology to our collaborators. 4. Assist in the selection and prioritization of the biologically most relevant leads. 5. Characterize leads in their appropriate cellular assays. 6. Provide broad preclinical development support including pharmacology, chemistry, toxicology, pharmacokinetics, and pharmaceutics, for compounds matching the preclinical lead profile criteria of B-MS. 7. Advance compounds to IND submission and clinical development, if warranted.