Targets, Structures and Drugs (TSD)

靶标、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 以药物化学为先导的大分子靶标结构研究进展 使用动物模型进行优化、合理设计和临床前评估，包括自然发生 高度反映人类疾病的犬类模型。普渡癌症研究中心(PCCR) 在药物发现方面的学术领先地位以开发有效靶点的新型抑制剂为特征 由PCCR科学家提供。TSD的50名计划成员已将11种PCCR化合物带入人体 临床试验和37种化合物(上次审查时为24种)进入临床前评估，包括 对22条狗进行的PCCR导联和新技术的研究。我们在下一个赠款周期的目标是进一步提高 通过继续加强治疗用铅的开发来进行药物开发。TSD由三位联合领导人领导： David Thompson(药物化学集群领导)、Deborah Knapp(目标验证集群领导)和 John Tesmer(铅、化学和结构生物学集群)。TSD开发流水线进一步 自上次审查以来战略增加了24个新成员，从而加强了TSD计划 在药物开发流程的每个阶段都有强大的覆盖面。TSD计划的成员处于活动状态 NCI实验治疗-化学生物学联盟(Thompson，主任)的参与者 比较肿瘤学临床试验联合会(奇尔德里斯，普渡主任)，DARPA Make It(Thompson，联合 )，以及NIH T32分子生物物理学(Tesmer，主任)和药物发现培训补助金 (戴相龙联席董事)。在过去的资助期间，TSD的教职员工已经获得了970万美元的同行评议癌症- 相关支持；发表了505篇同行评审文章(25%影响较大)，其中14%是方案内文章 15%的方案间协作(49%的机构间协作)。此外，TSD的教职员工将他们的研究转化为 转化为可交付成果，包括53项专利和5家公司在最新的资金期。 为了促进我们推进PCCR先导化合物的目标，TSD计划：(1)从战略上 部署方案资金，以启动和支持新的方案间和方案内协作；(2) 利用普渡在低温电子显微镜(Cryo-EM)方面的优势，加强基于结构的药物设计和 目标验证；(3)进一步开发可扩展的PCCR引线的自动连续合成，使其能够 锅炉制造商健康创新(BHI)；(4)扩大犬自发性癌症模型的铅测试；以及(5) 通过创新培训激励癌症研究领域的科学带头人不断发展。我们会 通过招募顶尖科学家，特别是在药物发现、化学生物学、 和Cryo-EM，并通过TSD计划聚会和主办 我们教职员工感兴趣的有针对性的研讨会。

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.