Assay development and screening for molecular targets and discovery

与MTP和其他NCI科学家在分析开发和筛选方面的合作包括分析开发、HTS和专注于11个目标的特性研究。例如，生长抑制或增强分析的开发应用(例如，Tbata选择性地针对衰老细胞和抑制胸腺细胞中的生长停滞)、蛋白质-蛋白质相互作用(例如，抑制或增强Raf与致癌RAS的结合)、报告基因分析(例如，抑制PAX3-FOXO1驱动的表达)以及生化和生物物理分析(与MTP蛋白质化学和分子生物科合作)。HTS分析用于支持天然产品化学工作，即从当前或以前完成的HTS活动中确定的天然产品提取物中提纯和表征活性化合物。其中包括数百个化学项目，目前集中在8个基于细胞的和生化目标上。最后，该部门与NCI的科学家广泛合作，对HTS和天然产品化学中产生的活性化合物进行表征。这些努力包括标准的细胞生物学和生化评估，以及应用酵母化学遗传学平台来识别潜在的分子靶标。通过对PAX3-FOXO1和TRAIL(组蛋白脱乙酰酶1和蛋白质合成抑制剂作为TRAIL增敏剂的新观察)的HTS活动中的活性化合物的分析，已有重要的文献发表。此外，美国药品监督管理局继续支持MTP抗艾滋病毒蛋白质的发现和开发，在2020年继续进行全细胞/活病毒抗艾滋病毒检测以及COVID/SARS项目。

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.