Assay development and screening for molecular targets and discovery

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Collaborations with MTP and other NCI scientists for assay development and screening include assay development, HTS, and characterization studies focused on 11 targets. Examples include development application of growth inhibition or enhancement assays (examples include selective targeting of senescent cells and inhibition of growth arrest in thymus cells by Tbata), protein-protein interactions (e.g., inhibition or enhancement of binding of Raf to oncogenic Ras), reporter gene assays (e.g., inhibition of PAX3-FOXO1-driven expression) and biochemical and biophysical assays (in collaboration with the MTP Protein Chemistry and Molecular Biology Section). The HTS assays are utilized in support of natural product chemistry efforts, i.e., purification and characterization of active compounds from natural product extracts identified from current or previously completed HTS campaigns. These include hundreds of chemistry projects currently focused on 8 cell-based and biochemical targets. Finally, the section collaborates extensively with NCI scientists to characterize active compounds that arise from HTS and natural products chemistry. These efforts include both standard cell biological and biochemical evaluation as well as application of a yeast chemical genetics platform for identification of potential molecular targets. Significant publications have resulted from analysis of active compounds from HTS campaigns for PAX3-FOXO1 and TRAIL (novel observations on histone deacetylases1 and on protein synthesis inhibitors as TRAIL sensitizers). In addition, the ADSS has continued to support MTP anti-HIV protein discovery and development with continued whole-cell/live-virus anti-HIV assays as well as COVID/SARS projects in 2020.