Lead Development & Optimization Shared Resource

铅开发和优化共享资源（LDOSR）：摘要 铅开发和优化共享资源（LDOSR）是一个共享资源的大学 堪萨斯癌症中心（KUCC），由位于KU Lawrence West的三个组成实验室组成 校园：高通量筛选（HTS），药物化学（MDCM）和生物制药 创新和优化中心（BIOC）。LDOSR为KUCC成员提供优先访问， 通过高通量筛选、化合物命中优先排序， 二级体外确证性试验、医学化学优化、体外药理学试验、体内 药代动力学和用于体内临床前概念验证测试的药物递送制剂。的活动 涉及候选药物的生成、评估和优化的是一个迭代过程， 跨越多个科学学科。LDOSR的结构是为了在一个单一的， 易于访问的保护伞，由主任和项目经理团队监督，允许项目 在组件实验室之间无缝移动。根据每个项目的需求量身定制的全面计划 确保用户获得最相关的数据，以推进他们的项目。此外，LDOSR还提供 准备赠款提交和出版语言。在过去五年（2016-2020年），LDOSR已 支持了167个KUCC成员项目（约76%由同行评审资助）。LDOSR利用研究 历史上，通过国际公认的医药和制药行业， 由堪萨斯大学药学院进行的化学研究。除此之外， 来自前制药和CRO公司的行业经验丰富的科学家。LDOSR具有 成功地招募了具有行业和学术资格的顶尖科学家， 组件实验室LDOSR与转化研究副主任合作， 成立了药物发现和开发指导委员会。这种预防性研究的催化剂 为KUCC研究人员提供了一个论坛，以在化学/生物学界面上开发研究概念， LDO实验室的支持。LDOSR与推进医学创新研究所合作， 通过早期药物开发推进药物发现项目，积极开展和支持研究 进行首次人体临床试验所必需的。此外，LDOSR工作人员还在研究者发起的 试验指导委员会，该委员会促进在早期试验阶段评价开发候选人 由D3 ET研究计划进行的治疗试验。最后，用于确定 临床前基质中的药物和代谢物浓度转移至临床药理学共享 在GLP条件下在人体基质中进行交叉验证以支持早期阶段的资源 临床试验其结果是一个完全集成的，端到端的翻译研究功能，能够推进 由KUCC成员发明的新型癌症治疗药物进行临床试验。

LEAD DEVELOPMENT AND OPTIMIZATION SHARED RESOURCE (LDOSR): ABSTRACT The Lead Development and Optimization Shared Resource (LDOSR) is a shared resource of The University of Kansas Cancer Center (KUCC), composed of three component laboratories located on the KU Lawrence West Campus: High-Throughput Screening (HTS), Medicinal Chemistry (MDCM) and the Biopharmaceutical Innovation and Optimization Center (BIOC). LDOSR provides preferred access to KUCC members to accelerate projects from drug-target discovery through high-throughput screening, compound hit prioritization, secondary in vitro confirmatory assays, medical chemistry optimization, in vitro pharmacology testing, in vivo pharmacokinetics, and drug delivery formulations for in vivo preclinical proof-of-concept testing. The activities involved with the generation, evaluation, and optimization of drug candidates is an iterative process that crosses several scientific disciplines. The LDOSR has been structured to optimize services under a single, easy-to-access umbrella, with oversight from the Director and a team of project managers, allowing projects to move seamlessly between component laboratories. Comprehensive plans tailored to fit each project’s needs ensure users get the most relevant data to move their projects forward. Additionally, the LDOSR offers drop-in ready grant submission and publication language. Over the past five years (2016-2020), the LDOSR has supported 167 KUCC member projects (~76% were peer-review funded). The LDOSR leverages research infrastructure established, historically, through internationally recognized medicinal and pharmaceutical chemistry research conducted by the University of Kansas School of Pharmacy. Added to this is the availability of industry experienced scientists from former area Pharma and CRO companies. The LDOSR has successfully recruited top-notch scientists with industry and academic qualifications to lead and staff the three component laboratories. The LDOSR, working with the Associate Director for Translational Research, established the Drug Discovery and Development Steering Committee. This translational-research catalyst provides a forum for KUCC investigators to develop research concepts at the chemistry/biology interface with support from the LDO laboratories. The LDOSR partners with The Institute for Advancing Medical Innovation to advance drug discovery projects through early drug development, actively conducting and supporting studies necessary to enable first-in-human clinical trials. Additionally, LDOSR staff serve on the Investigator-Initiated Trial Steering Committee, which facilitates evaluation of development candidates in early phase experimental therapeutics trials conducted by the D3ET research program. Lastly, bioanalytical methods for determination of drug and metabolite concentrations in preclinical matrices, are transferred to the Clinical Pharmacology Shared Resource where they are cross-validated in human matrices under GLP conditions to support early phase clinical trials. The result is a fully integrated, end-to-end translational research function capable of advancing novel cancer therapeutic agents invented by KUCC members to clinical trials.