Extraction, Dereplication, Isolation Chemistry, and Biological Evaluation

提取、去重复、分离化学和生物学评估

• 批准号: 7302061
• 负责人: Alan Douglas Kinghorn
• 金额: $ 21.48万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7302061
• 关键词: Antineoplastic Agents; Apoptosis; Biochemistry; Biological Assay; Biological Factors; Cancer Cell Growth; Cell Line; Cells; Cellular Assay; Chemistry; Chicago; Clinical; Collaborations; Crude Extracts; Cyanobacterium; Cytostatics; Development; Drug Kinetics; Evaluation; Fractionation; Growth Factor; Human; Illinois; Institutes; Lead; Malignant Neoplasms; Methylation; Modeling; Molds; Molecular; Molecular Target; Mus; Numbers; Ohio; Pathway interactions; Pharmacologic Substance; Pharmacology; Pharmacy (field); Plant Sources; Protein Tyrosine Kinase; Range; Research; Research Institute; Resources; Screening procedure; Series; Signal Transduction; Technology; Testing; Toxicology; Tumor Cell Line; Universities; base; cytotoxic; drug discovery; high throughput screening; in vivo; in vivo Model; innovation; interest; new technology; novel; oncology; pre-clinical; programs; tumor; tumor xenograft

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.

与俄亥俄州立大学（OSU；项目 1；核心 B 和 D）合作，伊利诺伊大学 芝加哥（UIC；项目 2；核心 A）和三角研究中心（RTI；项目 3），核心 C Bristol-Myers 施贵宝 (B-MS) 计划鉴定和评估源自各种天然产物的新型抗癌药物 来源（植物、陆生蓝细菌和丝状真菌）。中医药研究院 B-MS 隶属于世界上最大的制药公司之一，坚定致力于： 在天然产物药物发现和开发方面拥有专门的资源和良好的记录。和 针对该项目，我们计划实现以下具体目标： 1. 测定粗提物和半提纯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 在不同肿瘤细胞系组中的活性有助于发现新型抗癌药物。 2. 测定各种分子中的粗提物和半提纯提取物以及分离的纯化合物 基于机制/目标驱动的肿瘤学筛选，有助于识别新型靶向抗癌药物 代理。 3. 通过在 B-MS 或 将高通量筛选 (HTS) 技术转让给我们的合作者。 4. 协助选择和优先考虑生物学上最相关的线索。 5. 在适当的细胞测定中表征先导化合物。 6. 提供广泛的临床前开发支持，包括药理学、化学、毒理学、 药代动力学和药剂学，用于符合 B-MS 临床前先导特征标准的化合物。 7. 如果有必要，将化合物推进 IND 提交和临床开发。