Core--Small molecule screening and medicinal chemistry

调节生物过程的小分子是分析复杂生物系统的有力工具，也是人类治疗的潜在先导化合物。在对抗辐射的背景下，高通量小分子筛选可能会导致更深入地了解辐射防护中涉及的生物过程，并发现新的辐射防护试剂。将建立一个小分子筛选和药物化学核心，为达纳法伯/哈佛辐射医学对策中心的参与者提供高通量筛选小分子文库的资源、仪器和专业知识。该核心将帮助支持一个设备齐全的筛查设施，配备具有开发和实施方面专门知识的人员。 高通量筛选，以及一个药物化学小组，将能够采取的第一步沿着药物开发途径。为此，核心将利用来自哈佛医学院（HMS）ICCB-朗伍德筛查设施的资源，并将与HMS的其他项目密切互动，这些项目具有相似的使命：生物防御和新发传染病（NSRB）区域卓越中心的国家筛查实验室和神经变性药物发现实验室（LDDN）。小分子筛选核心，通过ICCB-Longwood，将共享小分子库，有机化学专业知识，并与NSRB和LDDN使用计算资源。该核心将支持多个筛选平台，并将建立药物化学能力，以推动通过筛选确定的最有希望的命中药物 发展 小分子筛选和药物化学核心的具体目标是： 1.为所有中心参与者提供小分子HTS设施，用于筛选纯蛋白和基于细胞的分析系统， 2.为了促进发现小分子研究工具来研究辐射防护相关的生物过程， 3.提供药物化学专业知识，将感兴趣的“热门”化合物成熟为具有辐射防护活性的潜在新型治疗先导物。

Small molecules that modulate biological processes are powerful tools for analyzing complex biological systems, as well as potential lead compounds for human therapy. In the context of countermeasures against radiation, high-throughput small molecule screens could lead to a deeper understanding of the biological processes involved in radioprotection and to the discovery of new radioprotective reagents. A Small Molecule Screening and Medicinal Chemistry Core will be established to provide resources, instruments, and expertise for high-throughput screening of small molecule libraries for participants in the Dana Farber/Harvard Center for Medical Countermeasures against Radiation. The Core will help support a fully equipped screening facility, staffed by personnel with expertise in the development and implementation of high-throughput screens, as well as a medicinal chemistry group that will be able to take the first steps along a drug development pathway. To this end, the Core will leverage resources from the Harvard Medical School (HMS) ICCB-Longwood Screening Facility and will interact closely with other programs at HMS that share similar missions: the National Screening Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Disease (NSRB) and the Laboratory for Drug Discovery in Neurodegeneration (LDDN). The Small Molecule Screening Core, through ICCB-Longwood, will share access to small molecule libraries, expertise in organic chemistry, and use of computational resources with NSRB and LDDN. The Core will support multiple screening platforms and will establish a medicinal chemistry capability to advance the most promising hits identified by screening towards pharmaceutical development. The Specific Aims of the Small Molecule Screening and Medicinal Chemistry Core are: 1. to provide access for all Center participants to a small molecule HTS facility for screening pure protein and cell-based assay systems, 2. to facilitate the discovery of small molecule research tools to study radioprotection-relevant biological processes, 3. to provide medicinal chemistry expertise for maturation of interesting "hit" compounds into potential novel therapeutic leads with radioprotective activity.