Drug Development Core Shared Resource

项目摘要/摘要 药物开发核心(DDC)的使命是使最先进的药物开发变得可访问 而且UWCCC成员负担得起。创新疗法的开发是中国的优先研究领域 UWCCC战略计划，药物开发需要合成、计算和 分析化学。DDC中最重要的科学学科是最广泛的药物化学 有道理。DDC通过高通量筛选(HTS)提供化合物发现； 电子计算机虚拟筛选和建模；化合物识别和优先排序的化学信息学；化学 有效的、选择性的和药理上可行的化合物的合成；以及支持 UWCCC临床试验采用药代动力学(PK)和药效学(PD)分析。目标1是进步 UWCCC通过提供广泛的药物化学专业知识和 基础设施包括发现、合成化学、计算化学、分析化学和 化学预防和抗癌药物的药理学。DDC工作人员向UWCCC成员提供各方面的建议 实验设计和数据解释。高技能和经验丰富的员工是使用方面的专家 先进的微波有机合成、分析和制备高效液相色谱分析设备， 质谱学、组合闪光层析法、无针尖和基于针尖的液体处理机器人、化验 96到1536孔板读取器的量化，以及高吞吐量计算。目标2是支持 通过提供所需的分析化学专业知识，在UWCCC进行临床试验 研究药物的药代动力学和药效学特性，并为患者样本存储提供 所有样本的健壮和安全的数据库文档。DDC工作人员与临床密切协调 UWCCC的试验企业，包括参与癌症治疗发现和开发(CTD2) 组织和以疾病为导向的团队为UWCCC成员提供药物浓度和 任何临床底物上的生物标记物和来自临床试验的研究样本的存储。在目前的资金中 在此期间，该中心为394项世界水资源中心的研究提供了支持。目标3是培训UWCCC成员及其工作人员，以及 学生在药物开发流程和生产性应用方面最先进、维护良好 为他们的特定研究目标提供设备，并提供全天候访问这种专注于药物开发的途径 基础设施。对UWCCC的影响：DDC支持了128名UWCCC独特成员的研究 在目前的供资周期内，并配备了充足的工作人员和装备，以满足未来的药物开发需求 UWCCC成员。CCSG的持续支持将使经验丰富的DDC工作人员科学家能够 投入时间和专业知识与UWCCC成员就未来项目和推进当前项目进行咨询 沿着发展道路到临床的有希望的分子。

PROJECT SUMMARY / ABSTRACT The mission of the Drug Development Core (DDC) is to make state-of-the-art drug development accessible and affordable to UWCCC members. Development of innovative therapies is a priority area of research in the UWCCC Strategic Plan, and drug development requires specialized expertise in synthetic, computational, and analytical chemistry. The overarching scientific discipline in the DDC is medicinal chemistry in its broadest sense. DDC offers compound discovery by high throughput screening (HTS); computational chemistry for in silico virtual screening and modeling; chemical informatics to identify and prioritize compounds; chemical synthesis of potent, selective, and pharmacologically viable compounds; and analytical chemistry to support UWCCC clinical trials with pharmacokinetic (PK) and pharmacodynamic (PD) assays. Aim 1 is to advance UWCCC member drug development research by providing broad medicinal chemistry expertise and infrastructure encompassing discovery, synthetic chemistry, computational chemistry, analytical chemistry, and pharmacology of chemoprevention and anticancer agents. DDC staff advise UWCCC members in all aspects of experimental design and data interpretation. The highly-skilled and experienced staff are experts in the use of state-of-the-art equipment for microwave-facilitated organic synthesis, analytical and preparative HPLC, mass spectrometry, combi-flash chromatography, tip-less and tip-based liquid handling robotics, assay quantification in 96 through 1536-well plate readers, and high throughput computing. Aim 2 is to support clinical trials conducted at UWCCC by providing analytical chemistry expertise needed to evaluate the pharmacokinetic and pharmacodynamic properties of study drugs and to provide patient sample storage with robust and secure database documentation of all samples. DDC staff are tightly coordinated with the clinical trial enterprise at UWCCC including participation in the Cancer Therapy Discovery and Development (CTD2) group and the Disease Oriented Teams to support UWCCC members with assays for drug concentrations and biomarkers on any clinical substrate and storage of study samples from clinical trials. In the current funding period, the core provided support for 394 UWCCC studies. Aim 3 is to train UWCCC members, their staff, and students in drug development processes and the productive application of state-of-the-art, well-maintained equipment to their specific research goals and provide 24/7 access to this drug development focused infrastructure. Impact on UWCCC: The DDC has supported the research of 128 unique UWCCC members during the current funding cycle and is well-staffed and equipped to meet the future drug development needs of UWCCC members. Continued support from the CCSG will enable highly experienced DDC staff scientists to invest time and expertise in consulting with UWCCC members on future projects and on advancing current promising molecules along the development pathway to the clinic.