Assay adaptation is usually required for high throughput screening (HTS) of chemical diversity sources of interest to the investigator. Such sources may include "libraries" of individual or mixtures of known synthetic or natural compounds, as well as synthetic or biosynthetic combinatorial libraries, which are available from numerous commercial sources. Considerations of cost, speed and robustness usually require that laboratory assays be substantially modified for HTS, while retaining the essential biology. Requirements of robotic liquid handling, or employment of particular assay endpoint detection methods such as time-resolved fluorescence or fluorescence polarization may require additional changes to assay design. Such modifications are worked out in an interactive, collaborative fashion with the intramural project advocate. The MTDP continues to develop, integrate, and refine the hardware, software and biological capabilities required for HTS applications to discovery within the CCR, NCI. In addition to possible exploitation of commercial sources of chemical diversity, the MTDP and intramural collaborators have available for screening the non-discreet compound collections residing in NCI repositories under the purview of the NCI Developmental Therapeutics Program. Additional chemical diversity sources for MTDP collaborative discovery research include Display Technologies, and Natural Products. In particular, the NCI Natural Products Repository comprises a unique and extraordinary resource available to CCR, NCI investigators for molecularly targeted discovery research.
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