Frederick National Laboratory for Cancer Research, NCI, Maryland, United States
Abstract: Abstract: Natural products have a proven track record in use as anti-cancer and anti-infective agents. As of 2020 natural products (NP), NP pharmacophores, and NP mimics represented >40% of small molecule-based anti-cancer and anti-microbial drugs. However, accessing the potential of NPs in high-throughput screening (HTS) campaigns has been challenging due to the complexity of the crude NP extracts, the time necessary for follow-up isolation efforts, and indefinite capabilities for large-scale resupply. This has resulted in NP-based libraries being significantly underrepresented in most recent large-scale HTS programs.
The US National Cancer Institute’s Natural Product Extract Repository is one of the world’s largest, most diverse collections of natural products containing >230,000 unique extracts derived from plant, marine and microbial organisms. To address the challenges in screening NPs and encourage increased assay of NP chemical diversity, the NCI created a Program for Natural Product Discovery (NPNPD) which has developed an automated, high-throughput robotics platform that has created 500,000 samples and released them to the public for screening. In addition, automated secondary purification and structure elucidation systems were created that significantly decrease costs and timelines. This presentation will discuss the reasons for, challenges to, and mechanisms by which to increase the pace and efficiency of NP-based drug discovery.