STRUCT/FUNCT ANALYSIS OF ANTHRACYCLINE REDUCTION BY HUMAN CARBONYL REDUCTASE

人羰基还原酶还原蒽环类化合物的结构/功能分析

• 批准号: 7959934
• 负责人: Henry Charlier
• 金额: $ 10.27万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959934
• 关键词: Alcohol Oxidoreductases; Anthracyclines; Binding; Cardiotoxicity; Clinical; Computer Retrieval of Information on Scientific Projects Database; Disease; Drug Metabolic Detoxication; Drug resistance; Effectiveness; Funding; Grant; Human; Idaho; Institution; Intention; Link; Metabolism; Pathway interactions; Pharmaceutical Preparations; Process; Prostaglandins; Quinones; Research; Research Personnel; Resources; Risk; Role; Source; United States National Institutes of Health; Work; cancer therapy; design; inhibitor/antagonist; interest; neuroprotection; programs

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Carbonyl reductase (CR) catalyzes the NADPH-dependent reduction of a wide range of carbonyls. CR has been connected to several important processes including but not limited to quinone detoxification, neuroprotection, prostaglandin metabolism, and, of clinical interest, anthracycline metabolism. CR reduction of anthracyclines significantly impacts their use in the treatment of cancer as it has been linked to both drug resistance and cardiotoxicity mechanisms. Therefore, inhibition of CR in conjunction with anthracycline therapy offers the potential both to increase the effectiveness of the drugs and to decrease the risk of the associated cardiotoxicity. The major emphasis of this work is to better understand how CR recognizes the molecules to which it binds, be they substrates or inhibitors. Equipped with this information, drugs may be designed to control CR with the intention of reducing the risk of cardiotoxicity during anthracycline cancer treatment. Also, as the role of CR in other pathways is better understood, such drugs may be used to treat other diseases as well.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 羰基还原酶（CR）催化多种羰基的NADPH依赖性还原。CR与几个重要过程有关，包括但不限于醌解毒、神经保护、前列腺素代谢以及临床感兴趣的蒽环类药物代谢。蒽环类药物的CR降低显著影响其在癌症治疗中的应用，因为它与耐药性和心脏毒性机制有关。因此，抑制CR联合蒽环类药物治疗提供了增加药物有效性和降低相关心脏毒性风险的潜力。这项工作的主要重点是更好地了解CR如何识别它所结合的分子，无论是底物还是抑制剂。有了这些信息，药物可以被设计成控制CR，目的是降低蒽环类药物治疗期间心脏毒性的风险。此外，随着CR在其他途径中的作用得到更好的理解，这些药物也可用于治疗其他疾病。