A TRANSFERASE IN DISORAZOLE SYNTHASE

二甲拉唑合成酶中的转移酶

• 批准号: 8169903
• 负责人: IRIMPAN I MATHEWS
• 金额: $ 0.3万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169903
• 关键词: Antineoplastic Agents; Apoptosis; Binding; Catalysis; Cell Death; Cell Line; Cell division; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Epothilones; Funding; Grant; Institution; Lung; Microtubules; Multi-Drug Resistance; Ovarian; Paclitaxel; Pharmaceutical Preparations; Research; Research Personnel; Resources; Source; Transferase; Tubulin; United States National Institutes of Health; Vincristine; malignant breast neoplasm; polymerization

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. Microtubules have been an attractive target for anticancer drugs since the identification and use of taxols for the treatment of lung, ovarian, and breast cancers. Taxol binds to and stabilizes microtubules, resulting in an arrest in cell division and eventual cell death. Compounds identified more recently with a similar action to taxol are the epothilones and discodermolides, both of which are in clinical trials. The disorazole A1, one of 29 related macrocyclic polyketides from a strain of Sorangium cellulosum, has been shown to inhibit the polymerization of tubulin, inducing apoptosis at picomolar concentrations. In contrast to the vincristine group of drugs, disorazoles are effective against multidrug-resistant cell lines. The structural study is aimed at understanding the mechanism of the catalysis of a transferase in disorazole synthase.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 自鉴定和使用紫杉醇治疗肺，卵巢和乳腺癌以来，微管一直是抗癌药物的有吸引力的靶标。紫杉醇与微管结合并稳定，导致细胞分裂和最终的细胞死亡停滞。最近发现的化合物与紫杉醇类似的作用是肩hon酮和do固酸酯，这两种都在临床试验中。 已证明异唑A1是来自sorangium纤维素菌株的29个相关的大环聚酮化合物之一，可抑制微管蛋白的聚合，在皮摩尔浓度下诱导凋亡。 与葡萄球菌的药物组相反，异唑有效地针对多药耐药细胞系有效。 该结构研究旨在理解异唑合酶中转移酶催化的机制。