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

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。 现代药物发现结合了基于靶标的方法，其中选择大分子药物靶标（通常是蛋白质）。 目标的三维结构通常通过X射线晶体学确定，并且目标活性位点的详细三维坐标用于计算机筛选和初始先导化合物的设计。 后续目标：铅化合物结构用于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，并且具有足够高的质量成为药物。 我们目前的药物发现工作集中在治疗癌症，细菌性疾病和病毒性疾病，特别是丙型肝炎病毒的新靶点。 这些研究工作需要MAD/SAD数据收集时间超过我们PRT成员提供给我们的时间。 该提案概述了额外MAD时间的请求，以支持我们的药物发现工作。

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 efforts.