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Optimization and Investigation of Cruentaren A analogs

Cruentaren A 类似物的优化和研究

基本信息

批准号：
9454428
负责人：
Brian S J Blagg
金额：
$ 34.25万
依托单位：
UNIVERSITY OF NOTRE DAME
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-01 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9454428
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

项目摘要

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.

摘要非常需要开发治疗癌症的新方法。在这个应用程序中，我们已经确定了一个大环小分子，其对癌细胞相对于正常细胞表现出高差异选择性，开发这种分子的更简单的类似物，以最大限度地提高效率，并减少步骤的总数，这将可能导致用于治疗癌症的临床上有用的分子。此外，本发明还提供了一种方法，我们的目的是研究这些化合物在癌症的细胞和动物模型中表现出的活性，其目的是提供临床前数据以支持这些化合物用于转化开发。