Targets, Structures and Drugs (TSD)

靶点、结构和药物 (TSD)

• 批准号: 10223207
• 负责人: Mingji Dai
• 金额: $ 4.23万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-08 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10223207
• 关键词: Animal Model; Animals; Antineoplastic Agents; Area; Award; Basic Science; Biologic Development; Biological; Biological Response Modifier Therapy; Biology; Biophysics; Cancer Biology; Cancer Center Support Grant; Cancer Model; Canis familiaris; Chemical Structure; Chemicals; Clinical Sciences; Clinical Trials; Collaborations; Competence; Cryoelectron Microscopy; Development; Drug Design; Drug Targeting; Electrons; Evaluation; Faculty; Faculty Recruitment; Funding; Goals; Grant; Health; Human; Immunologics; Indiana University Cancer Center; Institution; Investigation; Investigational Therapies; Knowledge; Lead; Leadership; Legal patent; Malignant Neoplasms; Methodology; Mission; Modality; Modeling; Molecular; Molecular Structure; Movement; NCI Center for Cancer Research; Organic Synthesis; Paper; Participant; Peer Review; Pharmaceutical Chemistry; Pharmaceutical Preparations; Phase; Preclinical Testing; Process; Program Research Project Grants; Publications; Publishing; Purdue Cancer Center; Research; Research Personnel; Research Support; Resolution; Scientist; Secure; Structure; Synthesis Chemistry; Testing; Therapeutic; Training; Translating; United States National Institutes of Health; Universities; Validation; anti-cancer; anticancer research; base; cancer clinical trial; cancer therapy; clinical application; clinical center; comparative; computerized tools; design; drug development; drug discovery; high throughput screening; human disease; inhibitor/antagonist; innovation; inter-institutional; interest; lead optimization; member; new technology; novel; novel therapeutics; preclinical evaluation; preclinical study; programs; protein structure; recruit; research clinical testing; small molecule; structural biology; symposium; targeted agent; targeted treatment; therapeutic development; tool; tumor

Targets, Structures and Drugs (TSD) Research Program Project Summary The mission of the newly formed Targets, Structures, and Drugs (TSD) Program is to accelerate the development of novel therapies for cancer treatment through a pipeline that identifies lead compounds or macromolecular target structures, and progresses their development by medicinal chemistry lead optimization, rational design, and preclinical evaluation using animal models, including naturally occurring canine models that are highly reflective of human disease. Purdue Center for Cancer Research (PCCR) academic leadership in drug discovery is characterized by development of novel inhibitors for targets validated by PCCR scientists. TSD's 50 Program members have shepherded 11 PCCR compounds into human clinical trials and 37 compounds (up from 24 at the last review) into preclinical evaluation, including a total of 22 canine studies of PCCR leads and novel technologies. Our goal the next grant cycle is to further enhance drug development by continuing to enhance therapeutic lead development. The TSD is led by three co-leaders: David Thompson (Lead, Medicinal Chemistry cluster), Deborah Knapp (Lead, Target Validation cluster), and John Tesmer (Lead, Chemical and Structure Biology cluster). The TSD developmental pipeline is further strengthened by the strategic addition of 24 new members since the last review, giving the TSD Program robust coverage in each phase of the drug development pipeline. Members of the TSD Program are active participants in the NCI Experimental Therapeutics – Chemical Biology Consortium (Thompson, Director), NCI Comparative Oncology Clinical Trials Consortium (Childress, Purdue Director), DARPA Make It (Thompson, co- Director), as well as NIH T32 Training Grants in Molecular Biophysics - (Tesmer, Director) and Drug Discovery (Dai, co-Director). Over this last funding period, TSD faculty have secured $9.7 million in peer-reviewed cancer- related support; have published 505 peer-reviewed articles, (25 % high-impact) with 14% intra-programmatic and 15% inter-programmatic collaborations (49% inter-institutional). Further, TSD faculty translate their research into deliverables, including 53 patents and 5 companies during this latest funding period. To facilitate our goals of advancing PCCR lead compounds, the TSD program plans to: (1) strategically deploy programmatic funds to nucleate and support new inter- and intra-programmatic collaborations; (2) leverage Purdue's strength in cryo-electron microcopy (cryo-EM) to enhance structure-based drug design and target validation; (3) further develop scalable automated continuous synthesis of PCCR leads enabled by Boilermaker Health Innovations (BHI); (4) expand lead testing in canine spontaneous cancer models; and (5) inspire the continuing development of scientific leaders in cancer research through innovative training. We will further these goals by recruiting leading scientists, particularly in the areas of drug discovery, chemical biology, and cryo-EM and continue cultivating a transdisciplinary culture through TSD Program gatherings and by hosting targeted symposia of interest to our faculty.

目标，结构和药物（TSD）研究计划 项目摘要 新成立的目标、结构和药物（TSD）计划的使命是加速 通过鉴定先导化合物的管道开发癌症治疗的新疗法， 大分子靶向结构，并以药物化学为先导， 优化，合理设计和临床前评价使用动物模型，包括自然发生的 高度反映人类疾病的犬类模型。普渡大学癌症研究中心（PCCR） 在药物发现方面的学术领导作用的特点是为已验证的靶点开发新的抑制剂 PCCR的科学家们TSD的50名计划成员已经将11种PCCR化合物引入人体 临床试验和37种化合物（从上次审查的24种增加）进入临床前评价，包括总共 PCCR电极导线和新技术的22项犬研究。我们下一个赠款周期的目标是进一步加强 药物开发，继续加强治疗铅的发展。TSD由三位共同领导人领导： 大卫汤普森（负责人，药物化学集群），黛博拉克纳普（负责人，目标验证集群），和 John Tesmer（化学和结构生物学组组长）。TSD开发管道进一步 自上次审查以来，战略性增加了24个新成员，使TSD计划得到加强， 在药物开发管道的每个阶段都有强大的覆盖面。TSD计划的成员非常活跃 参加NCI实验治疗学-化学生物学联盟（Thompson，主任），NCI 比较肿瘤学临床试验联盟（奇尔德里斯，普渡大学主任），DARPA Make It（汤普森，共同 主任），以及NIH T32分子生物物理学培训赠款-（Tesmer，主任）和药物发现 (Dai，共同主任）。在这最后一个资助期间，TSD教师已经获得了970万美元的同行评审癌症- 相关支持;发表了505篇同行评审文章（25%影响力大），14%是方案内文章 15%的项目间合作（49%的机构间合作）。此外，TSD教师将他们的研究成果 在最近的资助期间，包括53项专利和5家公司。 为了促进我们推进PCCR先导化合物的目标，TSD计划计划：（1）战略性 部署方案资金，以促进和支持新的方案间和方案内合作;（2） 利用普渡大学在低温电子显微镜（cryo-EM）方面的优势，加强基于结构的药物设计， 目标验证;（3）进一步开发PCCR引线的可扩展自动化连续合成， Boilermaker Health Innovations（BHI）;（4）扩大犬自发性癌症模型中的铅测试;以及（5） 通过创新培训激励癌症研究领域科学领导者的持续发展。我们将 通过招募领先的科学家，特别是在药物发现，化学生物学， 和冷冻EM，并继续通过TSD计划聚会和举办跨学科文化 针对我们教师感兴趣的专题讨论会。