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的一部分，有助于长期（HEL）倡议结束成瘾，以加快科学解决方案，以了解疼痛的基础并增强临床疼痛管理。 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 medical chemistry discovery program beginning at the Exploratory开发结构活动关系的化学阶段（SAR）分析，合成，体外滥用，分布，新陈代谢，极端的制度和毒理学（ADMET），计算化学/计算机辅助药物发现（CADD）的存储和运输复合登录和运输，以支持贡献者Spigelman（UCLA），以开发出一种新型的治疗性治疗性治疗性痛苦。这将通过推进其小分子杂环的SAR/SPR利用其测定法和体外ADMET来识别针对药物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是基于潜在抑制剂的杂环支架合成新型配体。候选分子将进行分析，以评估与治疗环境中化合物的物理特性特别相关的标准，包括酶选择性和测试，以确定与关键代谢酶系统的潜在相互作用。目标是将项目推进到/不进行决策，并连续发展到每个选项阶段（启动铅和铅优化的开始）。该合同产生的数据将由Ninds，贡献者或赞助的研究人员使用，以支持调查新药（IND）应用的指示临床前活动。本合同努力的结果将是进一步开发的临床前候选化合物的基础，即制备IND申请时先进的PK和毒理学评估。