STRUCTURAL STUDIES ON KEY DRUG TARGETS: HUMAN KINASES AND NTP-BINDING PROTEINS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。现代药物发现结合了一种基于靶点的方法，即选择一个大分子药物靶点(通常是蛋白质)。目标的三维结构通常由X射线结晶学确定，目标活性中心的详细三维坐标用于电子筛选和初始先导化合物的设计。后续目标：使用铅化合物结构来指导下一系列铅化合物的设计。这个过程反复进行，直到先导化合物具有合适的性质，并具有足够高的质量来作为药物。我们目前的药物发现工作集中在治疗癌症、细菌疾病和病毒性疾病，特别是丙型肝炎病毒的新靶点上。这些研究工作需要的MAD/SAD数据收集时间超过了我们PRT成员提供给我们的时间。该提案概述了对额外疯狂时间的请求，以支持我们的药物发现e

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. Modern drug discovery incorporates a target-based approach, wherein a macromolecular drug target (typically a protein) is chosen. The three-dimensional structure of the target is determined, usually by x-ray crystallography, and the detailed three-dimensional coordinates of the target active site are used for in silico screening and the design of initial lead compounds. Subsequent target:lead-compound structures are used to guide the design of the next series of lead compounds. This process iterates until the lead compound has suitable properties and is of high enough quality to be a drug. Our current drug discovery efforts focus on novel targets for the treatment of cancer, bacterial diseases, and viral diseases, particularly hepatitis C virus. These research efforts require MAD/SAD data collection time in excess of the time provided to us by our PRT membership. This proposal outlines a request for additional MAD time to support our drug discovery e