Extraction, Dereplication, Isolation Chemistry, and Biological Evaluation

与俄亥俄州立大学(俄亥俄州立大学；项目1；核心B和D)合作，伊利诺伊大学在 芝加哥(UIC；项目2；核心A)和三角研究所(RTI；项目3)，位于百时美施贵宝C核心 施贵宝(B-MS)计划识别和评估从各种天然产品中提取的新型抗癌药物 来源(植物、陆生蓝藻和丝状真菌)。中国药学研究院 B-MS是世界上最大的制药公司之一的一部分，坚定地致力于， 在天然产物药物发现和开发方面的专门资源和经过证明的跟踪记录。使用 关于这一项目，我们计划实现以下具体目标： 1.测定粗提物和半纯化提取物以及分离的纯化合物的细胞毒性和/或细胞抑制作用 不同肿瘤细胞系的活性有助于发现新的抗癌药物。 2.对粗提物、半提纯提取物以及分离得到的各种分子的纯化合物进行了分析 基于机制/靶点驱动的肿瘤学筛选，以帮助识别新的靶向抗癌药物 探员们。 3.通过在B-MS或在B-MS上进行分析来支持活性成分的活性引导分级 将高通量屏幕(HTS)技术转移给我们的合作者。 4.协助挑选生物学上最相关的线索并确定其优先次序。 5.在适当的细胞分析中确定引线的特征。 6.提供广泛的临床前开发支持，包括药理学、化学、毒理学、 符合B-MS临床前铅分布标准的化合物的药代动力学和药剂学。 7.如果有必要，将化合物提交给IND并进行临床开发。

In collaboration with The Ohio State University (OSU; Project 1; Cores B and D), the University of Illinois at Chicago (UIC; Project 2; Core A), and Research Triangle Institute (RTI; Project 3), in Core C Bristol-Myers Squibb (B-MS) plans to identify and evaluate novel anticancer agents derived from various natural product sources (plants, terrestrial cyanobacteria, and filamentous fungi). The Pharmaceutical Research Institute of B-MS is part of one of the largest pharmaceutical companies in the world, with a strong commitment to, dedicated resources for, and a proven track record in natural product drug discovery and development. With respect to this project, we plan to carry out the following Specific Aims: 1. Assay crude and semi-purified extracts as well as isolated pure compounds for cytotoxic and/or cytostatic activity in a diverse tumor cell line panel to aid the discovery of novel anticancer agents. 2. Assay crude and semi-purified extracts as well as isolated pure compounds in various molecular mechanism based/target-driven oncology screens to aid in the identification of novel, targeted anticancer agents. 3. Support activity-guided fractionation of the active constituents either by performing the assays at B-MS or transferring the high throughput screen (HTS) technology to our collaborators. 4. Assist in the selection and prioritization of the biologically most relevant leads. 5. Characterize leads in their appropriate cellular assays. 6. Provide broad preclinical development support including pharmacology, chemistry, toxicology, pharmacokinetics, and pharmaceutics, for compounds matching the preclinical lead profile criteria of B-MS. 7. Advance compounds to IND submission and clinical development, if warranted.