Legacy continuation of the KU CMLD Mission

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集合，国立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资助机制下维护的，现已停止使用，因此有资格被视为本计划公告下的遗留资源。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提供超过7000种化合物。最令人兴奋的是，许多KU CMLD中心化合物已被确定为不同屏幕中的热门产品，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维持SMR，通过当前活跃的特定项目R01奖项（PAR-12 - 058）启用新的筛选，这意味着将继续识别新的命中。然而，研究人员的能力， 非商业性化合物是处置库的宝贵和独特资产，但由于这些化合物的供应日益减少，其中许多化合物已被耗尽，获取这些化合物的机会受到威胁。这种威胁对于纯样品（通常是粉末）尤其严重，这些样品对于初始筛选后的验证工作至关重要。我们建议通过本方案解决这些问题。我们的近期目标是为在SMR中发现筛选命中的科学家提供结构验证的定量质量控制样品以及化学相似的类似物进行验证。这将需要在科学推广方面持续努力，以最大限度地扩大这些活动的潜在客户群，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库合成和命中验证活动转变为可持续的努力，最终将得到项目特定研究补助金和客户退款的成本回收的支持。

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.