Assay development and screening for molecular targets and discovery

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Assay development efforts focus on the configuration, optimization and validation of high-throughput assays to screen pure compound libraries and natural product extracts for modulators of specific molecular and cellular targets and associated cellular phenotypes. The section also develops and applies assays to characterize active molecules in mechanism of action studies and to prioritize compounds for further advancement toward utilization as probes and therapeutics. Nine cell-based assays were developed (in addition to 4 biochemical assays developed in collaboration with the Protein Chemistry and Molecular Biology Section), 11 high-throughput screening (HTS) campaigns were performed and 12 assays were performed in support of natural products chemistry. Biological characterization studies were performed on numerous hits from completed HTS campaigns, including utilization of a chemical genomics platform to assess mechanisms of action of natural product modulators of transcriptional regulation and cytotoxicity. Natural products-focused HTS has also led to development of lead compounds being further assessed in pre-clinical models of drug uptake, immunoregulation, transcriptional regulation, as well as preclinical development of a mithramycin analog.