NCI Program for Natural Products Discovery - Cures

成就：目标1。创建新技术，建立一个增强的NP预分馏库，适用于现代高通量靶向筛选程序。-新的高通量天然产物化学基础设施已经在位于Ft. Detrick的Frederick校区的NCI建立、装备和实施。实施的技术每年可生产多达175,000个分离的天然产品样品，以及多达1,100,000个馏分的自动存储和分选，每年可电镀（384孔板）5,000,000个测试样品。- NPNPD帮助创建了新的机器人系统，增强了冻干能力，自动化净化和分析化学系统，液体处理系统以及这些自动化系统之间的集成机器人接口。- NPNPD编写了新的自动化程序代码，用于天然产品样品的创建，注释，存储，电镀干燥和纯化。-这些技术和项目已经成功转移到其他研究机构（密歇根大学、密西西比大学和南非比勒陀利亚大学）。目标2。利用新的方法和文库扩大可培养微生物的化学多样性。- NPNPD在弗雷德里克校区的NCI建立、装备并实施了新的设施和方法，用于高通量培养和提取微生物。- NPNPD通过与俄克拉何马大学公民科学项目签订合同，建立了一个图书馆，收藏了在美国各地收集的13,000种土壤真菌。NPNPD对所有这些样品进行了处理、拍照、培养并确定了ITS序列和分类。- NPNPD迄今已对NCI加入的真菌进行了100,000个单独培养瓶的冷冻，以保存和分配该资源。- NPNPD已完成从澳大利亚海洋科学研究所获得的6700种澳大利亚海洋微生物。-真菌的初始液体培养、提取和预分离方案已简化为实践。目标3。为世界各地的筛选中心提供预分离库，加速药物发现。- NPNPD到目前为止已经生产了450,000个预分离提取物，并在28,000个384孔板上镀了18,000,000个孔以供分发。- NPNPD已向公众提供326,000个单独的384孔板预分馏天然产品样品。到目前为止，NPNPD运送了450万份筛选样品（超过NCI天然产品库在过去40年历史中运送的NCI天然产品样品的总和）。- NPNPD迄今已收到并处理了60份来自世界各地研究机构的材料转移协议（mta）请求，以使这些中心能够筛选NPNPD预分馏天然产品样品。- NPNPD迄今已与全球研究机构完成了30个单独的mta（详细列表见附录部分）。- NPNPD于2018年在ACS化学生物学上发表了一篇关于这一特定目标的手稿，这是封面文章。目标4。为研究人员提供高通量筛选支持，以实现有针对性的发现工作。- NPNPD已与NIAID、NCATS、NCCIH、国防部和Astra Zeneca UK签订联合研究协议，利用NPNPD预分离文库开展联合药物发现工作。- NPNPD已经成功地为CCR、德克萨斯大学、爱荷华大学、范德比尔特大学、贝勒医学院、耶鲁医学院、沃尔特里德陆军研究所、NIAID和阿斯特拉捷利康的研究人员提供了多个屏幕支持。- NPNPD是比勒陀利亚大学（南非）资助的一个国际研究项目的参与者，该项目将使用NPNPD的技术开发一个非洲血统的片段库，在非洲、澳大利亚、印度、欧洲、英国和NCI进行筛选。- NPNPD在2020年的《天然产品报告》中发表了一篇关于这一特定目标的手稿，这是封面文章。目标5。提供更快的分析资源（隔离、结构解析、再供应）以加快转化过程。- NPNPD在位于德里克堡弗雷德里克校区的NCI创建、装备并实施了高通量二级净化和分析化学能力。- NPNPD创造了每周进行多达500次净化以及电镀和干燥10,000个亚组分样品的能力。- NPNPD已经成功地在CCR/NCI、Astra Zeneca和国防部的几个项目中利用了这种能力。- NPNPD生产并运送25000个从活性NPNPD馏分中提取的纯化亚馏分到筛选中心。- NCI已将这些技术转让给密西西比大学、比勒陀利亚大学、南非和瑞典。- NPNPD于2020年在ACS化学生物学上发表了一篇关于这一特定目标的手稿，这是封面文章。目标6。建立公共数据库和生物信息学平台，扩大投入，扩大影响。- NPNPD正在对传统天然产品数据库进行现代化改造，使其成为更现代、更容易兼容的数据库结构。这些数据库包括分类、数量、收集地点信息、来源生物的照片、史密森学会的代金券收集、运输记录、生物测定结果、分析化学文件(包括化学结构、核磁共振、- NPNPD已与史密森学会和NIH达成协议，将NCI天然产品代金券收藏作为永久保护的机构重要科学收藏。该协议包括公众获取代金券样本的方面。- NPNPD开发了自组织地图（SOM）生物信息系统，用于根据分析其生物活性对天然产物化学工作进行快速优先排序。- NPNPD于2021年在《分子肿瘤学》上发表了一篇关于这一特定目标的手稿，这是封面文章。

Accomplishments: Aim 1. Create new technologies to build an enhanced NP pre-fractionated library amenable to modern high-throughput targeted screening programs. -New high-throughput natural products chemistry infrastructure has been built, outfitted and implemented on the NCI at Frederick campus on Ft. Detrick. Implemented technologies enable the production of up to 175,000 fractionated natural product samples per year as well as the automated storing and sorting of up to 1,100,000 fractions and the plating (in 384-well plates) of 5,000,000 test samples per year. -The NPNPD has helped create new robotic systems, enhanced lyophilization capabilities, automated purification and analytical chemistry systems, liquid handling systems and integrated robotic interfaces between these automated systems. -The NPNPD has written code for new automation programs for the creation, annotation, storage, plating drying, and purification of natural product samples. -These technologies and programs have already been successfully transferred to additional research institutes (Univ. Michigan, Univ. Mississippi, and the University of Pretoria, S. Africa). Aim 2. Expand the chemical diversity available to the public from culturable microorganisms with new methods and libraries. -The NPNPD has built, outfitted and implemented new facilities and methods for the high-throughput cultivation and extraction of microorganisms at the NCI at Frederick campus on Ft. Detrick. -The NPNPD has created, through a contract with the University of Oklahoma Citizen Science Program a library of 13,000 individual soil fungi collected throughout the United States. The NPNPD has processed, photographed, cultured and determined the ITS sequence and taxonomy of all of these samples. -The NPNPD has so far cryo-vialed 100,000 individual culture vials of fungi accessioned by the NCI for preservation and distribution of this resource. -The NPNPD has completed acquisition of 6700 Australian marine microbes from the Australian Institute of Marine Science. -Initial liquid cultivation, extraction and prefractionation protocols for fungi have been reduced to practice. Aim 3. Provide the pre-fractionated library to screening centers worldwide to accelerate drug discovery. -The NPNPD has so far produced 450,000 pre-fractionated extracts and plated 18,000,000 wells on 28,000 384-well plates for distribution. -The NPNPD has made available to the public 326,000 individual pre-fractionated natural product samples in 384-well plates. -The NPNPD shipped 4,500,000 screening samples so far (more than the combined shipments of NCI natural product samples throughout the previous 40 year history of the NCI Natural Products Repository). -The NPNPD has so far received and processed 60 requests for material transfer agreements (MTAs) from research organization around the world to enable these centers to screen NPNPD pre-fractionated natural product samples. -The NPNPD has so far completed 30 individual MTAs with research institutions worldwide (see Appendix section for a detailed list). -The NPNPD published a manuscript on this specific aim in ACS Chemical Biology in 2018, it was the cover article. Aim 4. Provide high throughput screening support for researchers to enable targeted discovery efforts. -The NPNPD has entered into joint research agreements with NIAID, NCATS, NCCIH, the Department of Defense, and Astra Zeneca UK to pursue joint drug discovery efforts using NPNPD pre-fractionated libraries. -The NPNPD has successfully supported multiple screens for researchers at the CCR, Univ. of Texas, Univ. of Iowa, Vanderbilt Univ., Baylor College of Medicine, Yale Medical School, Walter Reed Army Institute of Research, NIAID, and Astra Zeneca. -The NPNPD is a participant in a funded international research program let by University of Pretoria (S. Africa) which will use NPNPD technologies to develop a library of fractions of African origin to be screened in Africa, Australia, India, Europe, the United Kingdom and the NCI. -The NPNPD published a manuscript on this specific aim in Natural Product Reports in 2020, it was the cover article. Aim 5. Provide faster analytical resources (isolation, structure elucidation, re-supply) to expedite translational pipelines. -The NPNPD has created, outfitted and implemented high-throughput secondary purification and analytical chemistry capabilities at the NCI at Frederick campus on Ft. Detrick. -The NPNPD has created the capability to perform up to 500 purifications together with plating and drying of 10,000 sub-fraction samples per week. -The NPNPD has successfully utilized this capability on several programs with the CCR/NCI, Astra Zeneca and the Department of Defense. -The NPNPD produced and shipped 25,000 purified subfractions derived from active NPNPD fractions to screening centers. -The NCI has transferred these technologies to the University of Mississippi and University of Pretoria, S. Africa, and Sweden. -The NPNPD published a manuscript on this specific aim in ACS Chemical Biology in 2020, it was the cover article. Aim 6. Establish a public database and bioinformatics platform to broaden input and expand impact. -The NPNPD is in the process of modernizing legacy natural product databases to bring them into more modern and easily compatible database structures. These databases include information on taxonomy, amount, collection location information, photographs of source organisms, voucher collections at the Smithsonian Institution, shipping records, bioassay results, analytical chemistry files (including chemical structures, NMR, IR and MS files) etc. -The NPNPD has reached agreement with the Smithsonian Institution and NIH to include the NCI Natural Product Voucher Collection as an Institutionally Significant Scientific Collection to be protected in perpetuity. This agreement includes aspects of public access to voucher specimens. -The NPNPD has developed Self-Organizing Map (SOM) bioinformatic systems for the rapid prioritization of natural products chemistry efforts based on analysis of their biological activity. -The NPNPD published a manuscript on this specific aim in Molecular Oncology in 2021, it was the cover article.