Assay development and screening for molecular targets and discovery

分析开发工作的重点是高通量分析的配置、优化和验证，以筛选用于特定分子和细胞靶标及相关细胞表型调节器的纯化合物文库和天然产品提取物。该部分还开发和应用分析方法来表征作用机制研究中的活性分子，并优先考虑化合物作为探针和治疗药物的进一步发展。开发了9个基于细胞的分析(除了与蛋白质化学和分子生物科合作开发的4个生化分析)，开展了11个高通量筛选(HTS)活动，并进行了12个分析，以支持天然产品化学。对已完成的HTS活动中的许多命中进行了生物学特性研究，包括利用化学基因组学平台来评估转录调节和细胞毒性的天然产物调节剂的作用机制。以天然产物为重点的HTS还导致了先导化合物的开发，在药物摄取、免疫调节、转录调节以及米曲霉素类似物的临床前开发模型中进一步评估了先导化合物的开发。

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.