Natural Products Support Group, Leidos Biomedical Research, Inc. , Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute , Frederick , Maryland 21702-1201 , United States.
Data Management Services, Inc. , Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute , Frederick , Maryland 21702-1201 , United States.
ACS Chem Biol. 2018 Sep 21;13(9):2484-2497. doi: 10.1021/acschembio.8b00389. Epub 2018 Jun 13.
The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural product discovery technologies and facilitate the discovery of structurally defined, validated lead molecules ready for translation will create a prefractionated library from over 125,000 natural product extracts with the aim of producing a publicly-accessible, HTS-amenable library of >1,000,000 fractions. This library, representing perhaps the largest accumulation of natural-product based fractions in the world, will be made available free of charge in 384-well plates for screening against all disease states in an effort to reinvigorate natural product-based drug discovery.
美国国立癌症研究所 (NCI) 的天然产物库是世界上最大、最多样化的天然产物收藏之一,其中包含了超过 23 万种独特的提取物,这些提取物来自世界各地生物多样性丰富的地区的植物、海洋和微生物。重要的是,这个国家资源可供研究界用于提取物的筛选和生物活性天然产物的分离。然而,尽管天然产物在药物发现方面取得了成功,但提取物在液体处理系统中的兼容性问题、延长的时间表使得基于天然产物的药物发现工作复杂化以及存在泛分析干扰化合物,这些问题都降低了人们对靶向分析系统中粗天然产物提取物文库进行高通量筛选 (HTS) 的热情。为了解决这些限制,NCI 天然产物发现计划 (NPNPD) 是一个新启动的国家计划,旨在推进天然产物发现技术,并促进具有结构定义、验证的先导分子的发现,以准备转化,该计划将从超过 125,000 种天然产物提取物中创建一个预分馏文库,目标是生成一个可供公众使用的、可进行 HTS 的超过 1,000,000 个馏分的文库。这个文库可能是世界上最大的天然产物基馏分积累之一,将以 384 孔板的形式免费提供,用于针对所有疾病状态进行筛选,以重新激发基于天然产物的药物发现。