Legacy continuation of the KU CMLD Mission

KU CMLD 使命的延续

• 批准号: 8753214
• 负责人: THOMAS EDWARD PRISINZANO
• 金额: $ 54.06万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8753214
• 关键词: Acute; Address; Award; Back; Biological; Biological Assay; Biology; Biomedical Research; Charge; Chemicals; Client; Clinical Trials; Collection; Communities; Development; Elements; Ensure; Evaluation; Funding; Funding Mechanisms; Funding Opportunities; Future; Goals; Kansas; Libraries; Library Collection Development; Liquid Chromatography; Maintenance; Methodology; Methods; Metric; Mission; Modeling; Molecular Bank; NIH Program Announcements; National Institute of General Medical Sciences; Pharmaceutical Chemistry; Powder dose form; Preparation; Process; Public Sector; Publications; Publishing; Quality Control; Recovery; Research; Research Personnel; Research Project Grants; Resources; Sampling; Scientist; Staging; Structure; Testing; United States National Institutes of Health; Universities; Validation; analog; base; cost; drug discovery; high throughput screening; interest; member; milligram; novel; operation; outreach; programs; public health relevance; repository; screening; small molecule; small molecule libraries

DESCRIPTION (provided by applicant): To provide academic researchers with high-quality compound collections for biological screening, the National Institute of General Medical Sciences established the Chemical Methodologies and Library Development (CMLD) Network and charged it with developing new ways of creating libraries and providing them to the SMR. The CMLD network was maintained under a R41 funding mechanism and has been discontinued, making it eligible for consideration as a legacy resource under the present program announcement. As part of the CMLD network, the University of Kansas CMLD center was responsible for developing numerous chemical methods and for providing >7000 compounds to the SMR. Most excitingly, numerous KU CMLD center compounds have been identified as hits in diverse screens, with a few progressing to full-blown development efforts currently underway. The NIH plans to maintain the SMR for the foreseeable future, with new screens being enabled by currently active, project-specific R01 awards (PAR-12-058), meaning that new hits will continue to be identified. However, the ability of researchers to have continued access to non-commercial compounds, which constitute a valuable and unique asset of the repository, is threatened by diminishing supplies of these compounds, many of which have been depleted. This threat is particularly acute with respect to pure samples (generally powders) that are essential for validation efforts following the initial screen. We propose to address these concerns through the present program. Our near-term goal is to supply scientists who have uncovered screening hits in the SMR with structurally validated quantitatively quality-controlled samples of the hit of interest as well as chemically similar analogs for validation efforts. This wll require a sustained effort in scientific outreach to maximize the potential client base for these activities as well as technical maintenance of our synthetic and compound purification/management capabilities Our long-term goal is to transform our library synthesis and hit validation activities into a sustainable effort that will eventually be supported by cost recovry from project-specific research grants and charge-backs to clients.

描述(由申请人提供)：为了向学术研究人员提供用于生物筛选的高质量化合物收藏，国家普通医学科学研究所建立了化学方法学和图书馆开发(CMLD)网络，并负责开发创建图书馆的新方法并将其提供给SMR。CMLD网络是在R41供资机制下维持的，并已停止使用，使其有资格作为本方案公告所述的遗留资源予以考虑。作为CMLD网络的一部分，堪萨斯大学CMLD中心负责开发多种化学方法，并向SMR提供7000种化合物。最令人兴奋的是，许多KU CMLD中心化合物已经在不同的屏幕上被确定为热门，其中一些正在进行全面的开发工作。NIH计划在可预见的未来保持SMR，目前活跃的、特定于项目的R01奖项(PAR-12-058)将启用新的屏幕，这意味着将继续识别新的热门歌曲。然而，研究人员的能力继续 非商业性化合物是储存库的一项宝贵而独特的资产，但由于这些化合物的供应不断减少，其中许多已经耗尽，对这些化合物的获取构成了威胁。这一威胁对于初始筛查后的验证工作至关重要的纯样品(通常是粉末)尤其严重。我们建议通过目前的方案来解决这些关切。我们的近期目标是为在SMR中发现筛选命中的科学家提供感兴趣的命中的结构验证、定量质量控制的样本，以及用于验证工作的化学上类似的类似物。这将需要在科学推广方面的持续努力，以最大限度地扩大这些活动的潜在客户基础，以及对我们的合成和化合物纯化/管理能力进行技术维护。我们的长期目标是将我们的图书馆合成和验证活动转变为一项可持续的努力，最终将得到来自特定项目研究赠款和客户退款的成本回收的支持。