Huryn Donna M, Cosford Nicholas D P
Pittsburgh Molecular Libraries Screening Center, University of Pittsburgh, Pittsburgh, PA 15260 and Penn Center for Molecular Discovery, University of Pennsylvania, Philadelphia, PA 19104, USA.
San Diego Center for Chemical Genomics, Burnham Institute for Medical Research, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Annu Rep Med Chem. 2007;42:401-416. doi: 10.1016/S0065-7743(07)42026-7. Epub 2007 Nov 7.
The NIH Molecular Libraries Screening Center Network (MLSCN) is a subset of the Molecular Libraries Initiative (MLI) component of the NIH Roadmap for Medical Research. The ultimate goal of the MLSCN and the MLI is to expand the availability, flexibility, and use of small-molecule chemical probes for basic research. A number of aspects of the MLSCN make this initiative unique from other academic screening center. First, all researchers have access to the screening centers through the NIH X01 and R03 funding mechanisms. Second, because of the diverse source of assays and the wide expertise available within the MSLCN, specific biological systems investigated and screened will include: (1) "high risk" targets-that is, proteins or biological systems whose function is unknown; (2) targets implicated in orphan diseases or diseases not typically addressed by the private sector; (3) novel or uncommon assay systems; and (4) "non-druggable" targets, such as inhibitors of aggregation and protein-protein interactions. Third, the small molecule screening library contains structures not typically found in commercial collections or those housed in pharmaceutical companies. Fourth, as the goal of the MLSCN is to develop selective chemical probes and small molecule tools that will interrogate novel biochemical pathways, the criteria for an acceptable class of molecules is broader for the MLSCN than for those involved in drug discovery and development. Fifth, is the inclusion of integral medicinal chemistry within each MLSCN Center that allows the network to produce chemical probes with particular properties, rather than simply identifying apparent activities from the screening collection.
美国国立卫生研究院分子文库筛选中心网络（MLSCN）是美国国立卫生研究院医学研究路线图分子文库计划（MLI）的一个子集。MLSCN和MLI的最终目标是扩大小分子化学探针在基础研究中的可及性、灵活性和应用。MLSCN的多个方面使该计划有别于其他学术筛选中心。首先，所有研究人员都可通过美国国立卫生研究院的X01和R03资助机制使用筛选中心。其次，由于检测方法来源多样且MLSCN内具备广泛的专业知识，所研究和筛选的特定生物系统将包括：（1）“高风险”靶点，即功能未知的蛋白质或生物系统；（2）与罕见病或私营部门通常不涉及的疾病相关的靶点；（3）新颖或不常见的检测系统；以及（4）“不可成药”靶点，如聚集抑制剂和蛋白质-蛋白质相互作用抑制剂。第三，小分子筛选文库包含商业收藏或制药公司所没有的结构。第四，由于MLSCN的目标是开发能探究新生化途径的选择性化学探针和小分子工具，因此MLSCN对于可接受分子类别的标准比参与药物研发的机构更为宽泛。第五，每个MLSCN中心都纳入了完整的药物化学，这使得该网络能够生产具有特定性质的化学探针，而不仅仅是从筛选库中识别出明显的活性。
