Optimization and Investigation of Cruentaren A analogs

Cruentaren A 类似物的优化和研究

• 批准号: 10078544
• 负责人: Brian S J Blagg
• 金额: $ 35.3万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10078544
• 关键词: Animal Cancer Model; Antineoplastic Agents; Binding; Binding Sites; Cancer cell line; Cardiotoxicity; Cell Line; Cell model; Client; Clinical; Clinical Trials; Complex; Data; Development; Dose; Energy Metabolism; Enzymes; Exhibits; Frequencies; Generations; Goals; HSP 90 inhibition; Heat shock proteins; Heat-Shock Response; Hepatotoxicity; In Vitro; Individual; Investigation; Lead; Malignant Neoplasms; Maximum Tolerated Dose; Methods; Molecular Chaperones; Molecular Conformation; N-terminal; Natural Products; Normal Cell; Pathway interactions; Patients; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Preclinical Drug Development; Production; Protein Isoforms; Proteins; Reporting; Schedule; Signal Transduction; Structure; Structure-Activity Relationship; Time; Toxic effect; Translating; Translations; Warburg Effect; analog; anticancer activity; antitumor agent; base; cancer cell; cancer therapy; clinical application; clinical candidate; in vitro activity; in vivo; in vivo Model; in vivo evaluation; inhibitor/antagonist; nanomolar; neoplastic cell; novel; novel anticancer drug; novel lead compound; overexpression; pre-clinical; preclinical development; preclinical evaluation; protein degradation; protein folding; research clinical testing; side effect; small molecule; tumor

Abstract The development of new methods to treat cancer is greatly needed. In this application, we have identified a macrocyclic small molecule that exhibits high differential selectivity for cancer cells vs. normal cells and aim to develop more simplified analogs of this molecule in an effort to maximize efficiency as well as to decrease the overall number of steps, which will likely lead to clinically useful molecules for the treatment of cancer. In addition, we aim to interrogate the activity manifested by these compounds in both cellular and animal models of cancer, with the goal of providing preclinical data to support the use of such compounds for translational development.

抽象的 非常需要开发治疗癌症的新方法。在此应用程序中，我们确定了 大环小分子，对癌细胞与正常细胞表现出高差异选择性，旨在 开发该分子的更简化的类似物，以最大限度地提高效率并减少 步骤总数，这可能会产生临床上有用的癌症治疗分子。此外， 我们的目标是探究这些化合物在癌症细胞和动物模型中表现出的活性， 目标是提供临床前数据以支持此类化合物用于转化开发。