Mays Cancer Center at UT Health SA

项目概要-药物发现与结构生物学共享资源 药物发现和结构生物学共享资源（DDSB）是一个新的梅斯癌症中心（MCC）- 支持共享资源，结合全面的服务，以更好地满足MCC用户的需求。 DDSB的目的是为MCC研究人员提供最先进的癌症研究能力- 在原子和分子水平上的相关大分子，它们如何与其他大分子， 作为配体，并用于识别可以使用先进工具（如X射线）靶向它们的小分子 晶体学、核磁共振（NMR）和表面等离子体共振（SPR）以及高通量筛选 (HTS)技术-包括但不限于，基于细胞的表型高含量成像和纯化 基于组件的高温超导DDSB为MCC结束癌症的总体使命做出了重要贡献 通过提供整合结构生物学、分子表型和药物的综合平台， 发现，以扩大对癌症的病因学知识，发现癌症相关的目标，并确定潜在的 治疗学DDSB由四个集成模块组成：（a）小分子探针和药物发现， (b)NMR、（c）X射线晶体学和（d）大分子相互作用。每个模块都由一名专家领导， 该领域，与马修哈特，博士提供的所有模块的监督。根据项目，DDSB可以 进行涉及一个或多个模块的重点研究，或进行涉及所有模块的综合研究。 在上一个报告期（2014 - 2018年），DDSB与40个MCC成员合作，他们使用了总量的53% 服务时间在此期间，DDSB支持了20篇癌症相关出版物。DDSB活动还产生了 10个先导化合物的管道处于结构指导优化阶段，18个早期项目，约50% 其中预计将在两年内达到领先的优化。在下一个融资期结束时， 预计将向癌症研究人员提供5 - 8个新的经过审查的线索，准备进入临床前阶段。到 为了进一步实现其目标，DDSB将建立先进的X射线晶体学、高通量 筛选（包括靶向迄今为止"不可治疗"靶点的方法），以及定向癌症相关靶点 降解在下一个资助期内，我们希望DDSB继续推进我们对 这些研究旨在揭示驱动癌症的机制，并确定新的癌症治疗方法，以供未来临床使用。的 DDSB结合了多种能力，由于所需的成本， 仪器的维护，以及使用这些技术所需的专业知识的广度。因此，DDSB 对于MCC实现其战略目标，即从分子水平理解这些过程至关重要 将癌症转化为新的治疗方法。

Project Summary—Drug Discovery and Structural Biology Shared Resource The Drug Discovery and Structural Biology Shared Resource (DDSB) is a new Mays Cancer Center (MCC)- supported Shared Resource that combines comprehensive services to better meet the needs of MCC users. The purpose of the DDSB is to provide state-of-the-art capabilities to MCC investigators for the study of cancer- related macromolecules at the atomic and molecular levels, how they interact with other macromolecules such as ligands, and for identification of small molecules that can target them using advanced tools such as X-ray crystallography, nuclear magnetic (NMR) and surface plasmon resonance (SPR), and high-throughput screening (HTS) technologies – including, but not limited to, cell-based phenotypic high-content imaging-based and purified component-based HTS. The DDSB makes critical contributions to the MCC’s overarching mission to end cancer by providing a comprehensive platform that integrates structural biology, molecular phenotypes, and drug discovery to expand knowledge on the etiology of cancer, discover cancer-relevant targets, and identify potential therapeutics. The DDSB is composed of four integrated modules: (a) Small Molecule Probe and Drug Discovery, (b) NMR, (c) X-ray Crystallography, and (d) Macromolecular Interactions. Each module is led by an expert in that field, with oversight of all modules provided by Matthew Hart, Ph.D. Depending on the project, DDSB can perform focused studies involving one or more modules, or perform integrative studies involving all modules. During the last reporting period (2014-2018), the DDSB worked with 40 MCC members who used 53% of total service time. In this period, the DDSB supported 20 cancer-related publications. DDSB activities also generated a pipeline of 10 lead compounds in the structure-guided optimization stage and 18 early-stage projects, ~50% of which are expected to reach lead optimization within two years. At the end of the next funding period we expect to have delivered 5-8 new vetted leads, ready to move into preclinical stages, to cancer investigators. To further its goals, the DDSB will establish advanced novel tools for X-ray crystallography, high-throughput screening (including approaches that target heretofore “undruggable” targets), and directed cancer-related target degradation. During the next funding period, we expect the DDSB to continue advancing our understanding of mechanisms that drive cancers and identifying novel cancer therapeutics to be tested for future clinical use. The DDSB unites multiple capabilities challenging for individual investigators to pursue because of the cost, required maintenance of the instrumentation, and breadth of expertise needed to use these technologies. Thus, the DDSB is essential for the MCC to achieve its strategic goal of translating a molecular understanding of the processes that underlie cancer into novel therapies.