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帮助结束长期成瘾（HEAL）计划的一部分，旨在加速科学解决方案，以了解疼痛的基础并加强临床疼痛管理。 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）提供全方位服务的设施和工作人员，他们将支持药物化学发现计划，从探索性化学阶段开始，开发结构活性关系（SAR）分析和设计，合成，体外吸收，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）和存储和运输的化合物物流，以支持贡献者Spigelman（UCLA）开发一种有效治疗口腔癌疼痛的新疗法。这将通过利用其测定和体外ADMET推进其小分子杂环起始化合物的SAR/SPR来实现，以鉴定针对物质使用障碍的靶酶的新型选择性抑制剂。我们的药物发现方法将是合成基于杂环骨架的新型配体，这些配体是有效的抑制剂。 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，包括酶选择性和确定与关键代谢酶系统潜在相互作用的测试。目标是推进项目的进行/不进行决策，并连续推进到每个选项阶段（开始销售线索启动和销售线索优化启动）。 本合同生成的数据将由NINDS、贡献者或申办的研究者使用，以支持临床前活动中的试验性新药（IND）申请。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，在准备IND申请时进行先进的PK和毒理学评价。