NCI Program for Natural Products Discovery - Cures

成就： 目标 1. 创造新技术来构建增强的 NP 预分级文库，以适应现代高通量靶向筛选计划。 -新的高通量天然产物化学基础设施已在美国国家癌症研究所 (NCI) 弗雷德里克堡 (FT. Frederick) 校区建成、配备和实施。德特里克。所采用的技术每年可生产多达 175,000 个分离的天然产物样品，以及自动存储和分类多达 1,100,000 个组分，以及每年 5,000,000 个测试样品的电镀（在 384 孔板中）。 - NPNPD 帮助创建了新的机器人系统、增强的冻干能力、自动纯化和分析化学系统、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 为新的自动化程序编写了代码，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. 通过新方法和库扩大公众可从可培养微生物中获得的化学多样性。 - NPNPD 在美国国家癌症研究所 (NCI) 弗雷德里克校区 (FT.) 建造、装备和实施了用于微生物高通量培养和提取的新设施和方法。德特里克。 - NPNPD 通过与俄克拉荷马大学公民科学项目签订的合同，创建了一个包含在美国各地收集的 13,000 种土壤真菌个体的图书馆。 NPNPD 对所有这些样本进行了处理、拍照、培养并确定了 ITS 序列和分类。 - NPNPD 迄今为止已冷冻保存了 100,000 个 NCI 加入的真菌个体培养瓶，用于保存和分发该资源。 - NPNPD 已完成从澳大利亚海洋科学研究所收购 6700 种澳大利亚海洋微生物。 -真菌的初始液体培养、提取和预分级方案已简化为实践。目标 3. 向世界各地的筛选中心提供预分级文库，以加速药物发现。 - NPNPD 迄今为止已生产了 450,000 份预分馏提取物，并将 18,000,000 个孔铺在 28,000 个 384 孔板上进行分配。 - NPNPD 已向公众提供 384 孔板中的 326,000 个预分级天然产物样品。 - 迄今为止，NPPND 已发货 4,500,000 个筛选样品（超过 NCI 天然产品存储库过去 40 年历史中 NCI 天然产品样品发货量的总和）。 - NPNPD 迄今已收到并处理了来自世界各地研究组织的 60 份材料转移协议 (MTA) 请求，使这些中心能够筛选 NPNPD 预分馏天然产品样品。 - NPNPD 迄今为止已与世界各地的研究机构完成了 30 个单独的 MTA（详细列表请参阅附录部分）。 - NPNPD 于 2018 年在 ACS Chemical Biology 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、国防部和英国阿斯利康 (Astra Zeneca UK) 签订联合研究协议，利用 NPNPD 预分馏库开展联合药物发现工作。 - NPNPD 已成功为 CCR、Univ. 的研究人员提供多个屏幕支持。德克萨斯大学爱荷华州、范德比尔特大学、贝勒医学院、耶鲁大学医学院、沃尔特·里德陆军研究所、NIAID 和阿斯利康。 - NPNPD 是比勒陀利亚大学（南非）资助的国际研究项目的参与者，该项目将利用 NPNPD 技术开发非洲来源的片段库，以便在非洲、澳大利亚、印度、欧洲、英国和 NCI 进行筛选。 - NPNPD 在 2020 年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（分离、结构阐明、重新供应）以加快转化流程。 - NPNPD 在英国金融时报弗雷德里克校区的 NCI 中创建、装备并实施了高通量二级纯化和分析化学能力。德特里克。 - NPNPD 已具备每周对 10,000 个亚组分样品进行多达 500 次纯化以及电镀和干燥的能力。 - NPNPD 已在 CCR/NCI、Astra Zeneca 和国防部的多个项目中成功利用了这一能力。 - NPNPD 生产了 25,000 个源自 NPNPD 活性组分的纯化亚组分，并将其运送到筛选中心。 -NCI 已将这些技术转让给密西西比大学和比勒陀利亚大学、南非和瑞典。 - NPNPD 在 2020 年 ACS Chemical Biology 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，将其纳入更现代、更容易兼容的数据库结构。这些数据库包括分类学信息、数量、收集地点信息、来源生物的照片、史密森学会的凭证收藏、运输记录、生物测定结果、分析化学文件（包括化学结构、NMR、IR和MS文件）等。 - NPNPD已与史密森学会和NIH达成协议，将NCI天然产品凭证收藏作为机构重要的科学收藏予以永久保护。该协议包括公众获取凭证样本的各个方面。 - NPNPD 开发了自组织图谱 (SOM) 生物信息系统，用于根据生物活性分析快速确定天然产物化学工作的优先级。 - NPNPD 于 2021 年在《分子肿瘤学》杂志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.