Chemical Biology Core

化学生物学核心

基本信息

批准号：
10333174
负责人：
Harshani R Lawrence
金额：
$ 16.22万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-02-18 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10333174
关键词：
Affinity Animals Antineoplastic Agents Automobile Driving Award Binding Biochemical Bioenergetics Biology Biophysics Blood CD8-Positive T-Lymphocytes Calorimetry Cancer Center Support Grant Cancer Control Cells Chemicals Chemistry Clinic Cloning Complex Consultations Cryoelectron Microscopy Crystallization Data Analyses Development Dimerization Drug Design Drug Interactions Drug Kinetics Drug Targeting Educational workshop Ensure Equipment Experimental Designs Formulation Funding Future Goals Grant Growth Immune response Infrastructure Knowledge Label Lead Libraries Ligands Machine Learning Malignant Neoplasms Mass Spectrum Analysis Metabolic Molecular Pathway interactions Peer Review Pharmaceutical Chemistry Pharmaceutical Preparations Phosphotransferases Prevention Production Property Protein Chemistry Protein Family Proteins Proteomics Publications Publishing Research Research Design Research Project Grants Research Support Resolution Roentgen Rays Scanning Science Services Signal Transduction Specificity Structure Structure-Activity Relationship Surface Plasmon Resonance Synthesis Chemistry Techniques Technology Titrations Training Training and Education Tyrosine Kinase Inhibitor Work X-Ray Crystallography X-Ray Medical Imaging anti-cancer base biophysical properties cancer cell chemical synthesis deep learning design drug discovery graft vs host disease improved inhibitor insight instrument instrumentation lead optimization member novel pre-clinical programs protein data bank protein function protein purification protein structure safety assessment safety study scale up screening small molecule small molecule libraries structural biology success tool transcription factor tumor tumorigenesis

项目摘要

PROJECT SUMMARY CHEMICAL BIOLOGY CORE The Chemical Biology Core (CBC) offers centralized cutting-edge technologies and expertise that facilitates and accelerates basic and drug discovery research. Established in 2004, the CBC has broad usage by the Programs of the Center, where CBC promotes the identification, synthesis and further development of small molecules and chemical probes specific for cancer targets, to elucidate underlying molecular mechanisms driving cancer and to support drug discovery efforts by providing state-of-the-art equipment and unique services. Specifically, the Scientific Co-Directors and staff of the CBC have broad knowledge and a wealth of expertise in synthetic and medicinal chemistry, chemical biology, biophysics, structural biology and drug discovery that supports the high-impact research of Members, and that expands the repertoire of research capabilities at Moffitt. To support the research efforts of Members, CBC activities are organized into three Specific Aims: Aim 1: To assist Members in study design, the synthesis of focused small molecule libraries, hit-to-lead optimization, and chemical probe syntheses. Aim 2: To provide services and infrastructure to study the structures and functions of proteins involved in cancer. Aim 3: To conduct training and education for Members and staff. CBC is integrally involved in, and has pivotally contributed to, the success of Member research projects. CBC chemistry services include synthesis of: 1) focused libraries for hit-to-lead-optimization; 2) chemical probes; 3) designed tagged small molecules for affinity-based chemical proteomics; and 4) medicinal chemistry and scale-up to provide pre-clinical compounds for efficacy, potency, selectivity and safety studies. CBC structural biology services include: 1) cloning, expression, and large-scale purification of target proteins; 2) protein crystallization; 3) high-resolution structure determination; 4) binding studies of protein-protein and protein- ligand/drug interactions; and 5) assisting with structure-guided design of small molecules. Since 2016, CBC supported 40 Members (a 54% increase from previous review), contributed to 21 new grant awards to Members, and supported 59 peer reviewed publications (7 high impact). In FY20 alone, CBC supported 25 Members (72% peer reviewed) in four of the five Programs (CBE 22%, CE 6%, MM 61%, IO 11%), representing 95% of all CBC usage. CBC will continue to provide exceptional chemical and structural biology services and technologies to Members in the upcoming cycle. Future CBC priorities are to: 1) generate in-house focused compound and fragment libraries for cell-based screening projects; 2) with BBSR and machine learning Members, develop new tools for drug design; 3) synthesize 13C-labeled metabolites that support metabolic flux analyses; 4) provide automated imaging for x-ray crystallization screens; and 5) expand support of cryo-electron microscopy studies.

项目摘要化学生物学核心化学生物学核心（CBC）提供了促进的集中式尖端技术和专业知识并加速基础和药物发现研究。 CBC成立于2004年，由中心的计划，CBC促进了小规模的识别，综合和进一步发展分子和化学探针针对癌症靶标的，以阐明驱动的基本分子机制癌症并通过提供最先进的设备和独特的服务来支持药物发现工作。具体而言，CBC的科学联合指导和员工具有广泛的知识和丰富的专业知识合成和药物化学，化学生物学，生物物理学，结构生物学和药物发现支持成员的高影响力研究，并扩大了莫菲特研究能力的曲目。为了支持成员的研究工作，CBC活动被组织为三个具体目标：目标1：为了协助成员进行研究设计，聚焦的小分子库的合成，命中率高优化和化学探针合成。目标2：提供服务和基础设施来研究涉及癌症蛋白质的结构和功能。目标3：对成员和员工进行培训和教育。 CBC在成员研究项目的成功方面积极参与，并为成员的成功做出了贡献。 CBC 化学服务包括：1）集中精力进行超优化的集中库； 2）化学探针； 3）为基于亲和力的化学蛋白质组学设计了标记的小分子； 4）药物化学和扩展以提供临床前化合物的功效，效力，选择性和安全性研究。 CBC结构生物学服务包括：1）靶蛋白的克隆，表达和大规模纯化； 2）蛋白质结晶; 3）高分辨率结构确定； 4）蛋白质蛋白质和蛋白质的结合研究配体/药物相互作用； 5）协助小分子的结构引导设计。自2016年以来，CBC 支持40名成员（比以前的审查增加了54％），为成员颁发了21个新的赠款奖励，并支持59个同行评审出版物（7个高影响力）。仅在20财年，CBC就支持25名成员（72％同行评审）在五个程序中的四个（CBE 22％，CE 6％，毫米61％，IO 11％）中，占所有CBC的95％用法。 CBC将继续提供非凡的化学和结构生物学服务和技术在即将到来的周期中的成员。未来的CBC优先级是：1）生成内部集中的化合物和用于基于细胞的筛查项目的碎片库； 2）与BBSR和机器学习成员一起开发新的药物设计工具； 3）合成13C标记的代谢产物，支持代谢通量分析； 4）提供 X射线结晶屏幕的自动成像； 5）扩大了冷冻电子显微镜研究的支持。