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.

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。 自从紫杉醇被发现并用于治疗肺癌、卵巢癌和乳腺癌以来，微管一直是抗癌药物的一个有吸引力的靶点。紫杉醇结合并稳定微管，导致细胞分裂停滞并最终导致细胞死亡。最近发现的具有与紫杉醇类似作用的化合物是埃博霉素和discodermolides，这两种化合物都在临床试验中。 地索拉唑A1是来自纤维堆囊菌菌株的29种相关大环聚酮化合物之一，已显示出抑制微管蛋白的聚合，在皮摩尔浓度下诱导细胞凋亡。 与长春新碱组药物相反，地索拉唑对多药耐药细胞系有效。 结构研究的目的是了解在异恶唑合成酶的转移酶的催化机制。