Scientific Core B The Oncology Drug Discovery (ODD) Division of Bristol-Myers Squibb (BMS), headed by Dr. Robert Kramer (Vice President Oncology Drug Discovery), will provide comprehensive molecular based, cellular, and in vivo evaluation of diverse natural products acquired from Professors W. Fenical, D.J. Faulkner and Y. Shimizu, our collaborators at the Scripps Institution of Oceanography and at the University of Rhode Island. This testing and development program will incorporate innovative high- throughput screening technologies against novel molecular targets in an effort to discover new, non-toxic molecules with highly specific mechanisms of action and in vivo efficacy. This approach will complement traditional cellular cytotoxic methods that have yielded first generation validated targets and have the potential to identify new cytotoxic targets with utility in cancer.
The specific aims are as follows: 1. Assay up to 4000 extracts and pure compounds/year for molecular interaction with specific oncogenes, hormonal pathways, angiogenic factors as well as cytotoxicity assays and traditional targets that are relevant to cancer therapy. 2. Assist in the selection and prioritization of the most biologically significant leads. 3. Support bioassay-guided fractionation of the active constituents either by performing the assays at BMS or transferring the high throughput screen (HTS) technology to collaborating scientists at Scripps Institution of Oceanography and the University of Rhode Island. 4. Provide biological vitro and in vivo development support to the lead compounds obtained from this program. In addition to efficacy studies additional parameters such as pharmacokinetics, oral bioavailability, toxicology and pharmaceutics will be induced as needed. 5. Through involvement of the Chemistry Group, carry out large-scale isolation and/or large-scale isolation and/or synthesis of lead candidates that match our preclinical lead profile (PLP) criteria.
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