Abstract
The Natural Products Repository (NPR) within the Natural Products Branch at NCI contains over 230,000 unique extracts derived from more than 75,000 plant, marine and microbial organisms. Importantly, this national resource is available to the research community for screening and isolation of crude extracts. However, compatibility issues that make them challenging for liquid handling systems, coupled with a high rediscovery and false-positive hit rate, reduce the enthusiasm for high-throughput screening of whole extract libraries in targeted assays systems. Furthermore, the chemical complexity inherent to whole extracts may mask active components present as minor metabolites. In order to address these limitations and make the Natural Products Repository more valuable to the extramural research community, we have developed methodology for the pre-fractionation of these whole extracts prior to biological testing. Notably, several marine, microbial and plant extracts examined in the NCI60 cancer cell line screen showed enhanced biological activity after fractionation. Additionally, these methods have recently been adapted for automation and high-throughput processing in order to build a library of pre-fractionated natural products from over 100,000 extracts from the Natural Products Repository.
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