MCSP TORFP NO. NIH-NINDS-20-03: KATRITCH (USC) - BASE EC (PAIN)

MCSP TORFP 编号

• 批准号: 10285409
• 负责人: KEITH BARNES
• 金额: $ 56.3万
• 依托单位: ALBANY MOLECULAR RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10285409
• 关键词: Biological Assay; Chemistry; Computer Assisted; Contracts; Data; Development; Drug Compounding; Enzymes; Evaluation; Excretory function; Goals; Grant; Health; Human; In Vitro; Individual; Institutes; Intellectual Property; Investigational Drugs; Investigational New Drug Application; Lead; Legal patent; Ligands; Logistics; Metabolic; Metabolism; Pain; Parkinson Disease; Pharmaceutical Chemistry; Phase; Preparation; Property; Regulation; Research Personnel; Rights; Services; Shipping; Stroke; Structure-Activity Relationship; System; Testing; Therapeutic; Toxicology; Treatment Efficacy; United States Dept. of Health and Human Services; United States National Institutes of Health; absorption; base; computational chemistry; design; direct application; drug discovery; indexing; inhibitor/antagonist; lead optimization; nervous system disorder; novel; novel therapeutics; pre-clinical; programs; scaffold; small molecule; therapeutic development

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 Mouradian/Disney (Rutgers/Scripps) to develop a novel therapeutic effective in Parkinson’s. 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 Parkinson’s. 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. The ultimate goal of the NIH programs served by this contract and of individual projects is to bring new drugs to market. To this end, the NIH has been granted a Determination of Exceptional Circumstances (DEC) to incorporate the Department of Health and Human Services Acquisition Regulation (HHSAR) clauses at 352.227-11, Patent-Rights-Exceptional Circumstances and 352.227-14, Rights in Data – Exceptional Circumstances, as part of any contract resulting from this solicitation. The HHSAR Clauses will enable the Contributors to retain control of the intellectual property for compounds created through the Medicinal Chemistry Support Program for Therapeutic Development (MCSP).

国家神经疾病和中风研究所（NINDS）和NIH蓝图 神经治疗学网络（BPN）http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm有需求 药物化学支持计划（MCSP）提供全方位服务的设施和工作人员， 支持从探索性化学阶段开始的药物化学发现计划， 开展构效关系（SAR）分析与设计、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）和化合物的储存和运输物流，以支持贡献者 Mouradian/迪士尼（罗格斯/斯克里普斯）开发一种新的治疗帕金森氏症有效。这将是 通过利用其小分子杂环起始化合物的SAR/SPR来实现 检测和体外ADMET，以鉴定靶酶的新型选择性抑制剂， 帕金森等我们的药物发现方法将是合成基于杂环的新型配体 支架是有效的抑制剂。候选分子将进行分析，以评估标准 具体涉及化合物在治疗环境中的物理化学性质，包括 酶的选择性和测试，以确定与关键代谢酶系统的潜在相互作用。的 目标是推进项目的进行/不进行决策，并在 继任（开始Hit-to-Lead和开始Lead Optimization）。本合同产生的数据 将由NINDS、贡献者或申办的研究者用于支持试验性新药 (IND)应用导向的临床前活动。本合同的努力结果将作为 推进临床前候选化合物的进一步开发，即，高级PK和毒理学 在准备IND申请时进行评估。 该合同所服务的NIH项目和单个项目的最终目标是为美国国家卫生研究院带来新的 药品进入市场。为此，国家卫生研究院已被授予确定例外情况， (DEC)纳入卫生与公众服务部采购条例（HHSAR） 第352.227-11条，专利权-例外情况和第352.227-14条，数据权利- 特殊情况，作为任何合同的一部分，从这个招标。HHSAR条款 将使贡献者能够保留对通过以下方式创建的化合物的知识产权的控制权： 药物化学治疗开发支持计划（MCSP）。