SPIGELMAN (UCLA) - MCSP- EXPLORATORY CHEMISTRY (EC)

SPIGELMAN（加州大学洛杉矶分校）- MCSP-探索化学（EC）

• 批准号: 10949389
• 负责人: MATTHEW SURMAN
• 金额: $ 66.21万
• 依托单位: ALBANY MOLECULAR RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-18 至 2028-02-17
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10949389
• 关键词: SPIGELMAN; UCLA; MCSP; EXPLORATORY; CHEMISTRY

This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to understand the basis of pain and enhance clinical pain management. The National Institute on Neurological Disorders and Stroke (NINDS) and the NIH Blueprint Neurotherapeutics Network (BPN) http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm have a need for the Medicinal Chemistry Support Program (MCSP) to provide a full-service facility and staff who would support a medicinal chemistry discovery program beginning at the Exploratory Chemistry phase to develop structure activity relationship (SAR) analysis and design, synthesis, in vitro absorption, distribution, metabolism, excretion and toxicology (ADMET), computational chemistry/Computer Aided Drug Discovery (CADD) and compound logistics of storage and shipping to support the Contributor Spigelman (UCLA) to develop a novel therapeutic effective in oral cancer pain. This will be achieved by advancing the SAR/SPR of their small molecule heterocyclic starting compound utilizing their assays and in vitro ADMET to identify novel, selective inhibitors of the target enzyme that are directed at substance use disorder. Our drug discovery approach will be to synthesize novel ligands based on the heterocyclic scaffold that are potent inhibitors. Candidate molecules will undergo profiling to assess criteria specifically related to the physicochemical properties of compounds in a therapeutic setting, including enzyme selectivity and tests to determine potential interactions with key metabolic enzyme systems. The goal is to advance the project to go/no go decisions and to progress to each of the Option phases in succession (start of Hit to Lead and start of Lead Optimization). The data generated from this contract will be used by NINDS, contributors or sponsored investigators in support of Investigational New Drug (IND) application directed preclinical activities. The results of the efforts of this contract will be the basis to advance preclinical candidate compounds for further development i.e., advanced PK and toxicological evaluation in preparation of IND filings.

这项研究是 NIH 帮助结束成瘾长期 (HEAL) 计划的一部分，旨在加快科学解决方案的速度，以了解疼痛的基础并加强临床疼痛管理。 美国国家神经疾病和中风研究所 (NINDS) 和 NIH 蓝图神经治疗网络 (BPN) http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm 需要药物化学支持计划 (MCSP) 提供提供全方位服务的设施和工作人员，他们将支持从探索化学阶段开始的药物化学发现计划，以开发结构活性关系 (SAR) 分析和设计、合成，吸收、分布、代谢、排泄和毒理学 (ADMET)、计算化学/计算机辅助药物发现 (CADD) 以及储存和运输的复合物流支持贡献者 Spigelman (UCLA) 开发口腔癌疼痛的新型治疗功效。我们的药物发现方法将是通过利用他们的检测和体外 ADMET 来提高小分子杂环起始化合物的 SAR/SPR，以识别针对药物滥用障碍的新型选择性靶酶抑制剂。合成基于杂环支架的新型配体，这些候选分子将进行分析，以评估与治疗环境中化合物的理化性质特别相关的标准，包括酶选择性和测试以确定与关键代谢酶目标的潜在相互作用。是推进项目进行或不进行决策，并连续进展到每个选项阶段（从命中到领先的开始和领先优化的开始）从本合同生成的数据将由 NINDS、贡献者或赞助研究人员支持研究性新药 (IND) 申请指导的临床前活动 该合同的努力结果将成为推进临床前候选化合物进一步开发的基础，即准备 IND 申请时进行高级 PK 和毒理学评估。