Chapter 26 The Molecular Libraries Screening Center Network (MLSCN): Identifying Chemical Probes of Biological Systems

Abstract

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.