STRUCTURAL STUDIES OF THERAPEUTIC TARGETS IN ONCOLOGY AND INFECTIOUS DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 近年来，尽管许多细菌的耐药性正在增加，但专注于广谱抗生素的药物研究大幅下降。阿斯利康正将其抗菌研究的重点放在具有广谱潜力的新靶点上，努力创造对临床菌株没有交叉耐药性的治疗剂。为了实现这些目标，在管道的所有阶段的大多数项目中都使用蛋白质结晶学来指导抑制剂的设计，通常使用来自多个细菌物种的同工酶。蛋白质结晶学在铅发现的早期阶段特别关键，特别是关于片段命中。阿斯利康波士顿研发中心的肿瘤学目标包括那些通过结构努力可以获得的目标。超过50%的肿瘤学流水线采用了基于结构的药物设计。靶点包括但不限于激酶，对其而言，来自内部和外部来源的丰富可用结构信息对于设计有效和选择性的抑制剂至关重要。

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. Pharmaceutical research focusing on broad-spectrum antibiotics has declined significantly in recent years, despite the fact that drug resistance is increasing in many bacterial species. AstraZeneca is focusing its efforts in antibacterial research on novel targets with broad spectrum potential in efforts to create therapeutic agents with no cross-resistance to clinical strains of bacteria. In order to obtain these goals, protein crystallography is being utilized in most projects at all stages of the pipeline to guide inhibitor design, often with isozymes from multiple bacterial species. Protein crystallography is especially critical in the earliest stages of lead discovery, particularly with regard to fragment hits.Oncology targets at AstraZeneca R&D Boston include those accessible by structural efforts. Structure-based drug design is utilized in more than 50% of the oncology pipeline. Targets include, but are not limited to kinases, for which the wealth of available structural information from internal and external sources is critical in the design of potent and selective inhibitors.