Drug Discovery & Structural Biology

.项目总结（见说明书）;药物发现和结构生物学核心（DDSB）是一个新的共享资源，支持COHCCC的基础，转化和临床科学家识别和开发小分子和大分子疗法。DDSB的首要目标是提供必要的科学资源，以协助化学生物学研究和基于分子的治疗方法的开发。DDSB包括几个科学学科，包括药物化学，生物聚合物合成，高通量筛选和X射线晶体学。而不是每个学科都有单独的核心，这些学科被合并到一个单元中，以实现药物开发的最大效率。这导致了独特的共享资源，协同工作，以实现癌症中心的基础和转化研究目标。提供的专门知识和服务的具体领域包括：合成有机化学、专门RNA和DNA的定制合成、分析开发、高通量筛选、蛋白质生产、生物物理表征和结构生物学。这些服务的合并为开发新的分子靶点提供了无缝的药物发现管道。DDSB核心是集中而灵活的，允许癌症中心成员单独或组合使用这些服务中的任何一种。DDSB的另一个重要组成部分是与Pis协商，开发试剂和检测方法，并获得初步结果，以支持癌症中心成员应用外部资助的提案。例如，DDSB开发了COH 29，一种新型小分子抑制剂，是PARP/核糖核苷酸还原酶双重拮抗剂，对BRCA 1缺陷型癌症具有有希望的活性。这项工作带来了新的投资回报率资金，我们的第一个GMP合成和临床试验候选药物完全在内部开发。总的来说，DDSB作为一个科学和知识中心，以跨学科的方法整合不同的学科，如分子建模，生物信息学和药理学，以开发治疗癌症的新药物。DDSB在这方面是独一无二的，因为它提供了一个完整的科学服务计划，并在学术环境中协调药物发现的努力。因此，Pis可以利用DDSB核心来追求以前在学术中心的一个站点无法获得的研究途径，从而加速COHCCC临床试验的化学生物学探针和分子靶向疗法的开发。

. PROJECT SUMMARY (See instructions); The Drug Discovery and Structural Biology Core (DDSB) is a new shared resource that supports the identification and development of small molecule and macromolecular therapeutics for the basic, translational and clinical scientists at COHCCC. The overarching goal of DDSB is to provide the necessary scientific resources to assist In chemical biology studies and development of molecularly-based therapeutics. DDSB comprises several scientific disciplines that include medicinal chemistry, biopolymer synthesis, high throughput screening, and X-ray crystallography. Rather than have separate cores for each, these disciplines are consolidated under one unit for maximum efficiency in drug development. This has resulted in unique shared resource that works in concert to achieve the basic and translational research goals of the Cancer Center. Specific areas of expertise and services provided include: synthetic organic chemistry, custom synthesis of specialized RNA and DNA, assay development, high-throughput screening, protein production, biophysical characterization and structural biology. The amalgamation of these services provides a seamless drug discovery pipeline for development of novel molecular targets. The DDSB core is focused yet flexible to allow Cancer Center members to use any one of these services individually or in combination. An additional significant component of the DDSB is to consult with Pis, develop reagents and assays, and obtain preliminary results to support the application of externally funded proposals by Cancer Center members. For example, the DDSB has developed COH29, a novel small-molecule inhibitor that is a dual PARP/rlbonucleotide reductase antagonist and has promising activity against BRCA1 deficient cancers. This work has led to new ROI funding and our first drug candidate for GMP synthesis and clinical trials developed completely in-house. Collectively, the DDSB serves as a scientific and intellectual hub for Integrating diverse disciplines such as molecular modeling, bioinformatics, and pharmacology in a transdisciplinary approach towards the development of new agents for the treatment of cancer. The DDSB Is unique in this capacity as it provides a complete program of scientific services and coordination of efforts for drug discovery in an academic setting. Thus, Pis can leverage the DDSB core for pursuing avenues of research not previously available at one site in an academic center, thereby accelerating the development of chemical biology probes and molecularly-targeted therapies for clinic trials at COHCCC.