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

MCSP TORFP 编号

• 批准号: 10416977
• 负责人: KEITH BARNES
• 金额: $ 131.41万
• 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 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10416977
• 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; 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; therapeutically effective

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).

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 有需要 为药物化学支持计划 (MCSP) 提供全方位服务的设施和工作人员 支持从探索化学阶段开始的药物化学发现计划 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) 以及存储和运输的复合物流以支持贡献者 Mouradian/迪士尼（罗格斯/斯克里普斯）将开发一种治疗帕金森病的新疗法。 通过利用其小分子杂环起始化合物提高 SAR/SPR 来实现 测定和体外 ADMET 来鉴定针对目标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的新型配体。 候选分子的支架将进行分析以评估标准。 与治疗环境中化合物的理化性质特别相关，包括 酶选择性和测试以确定与关键酶代谢系统的潜在相互作用。 目标是推进项目进行或不进行决策，并进展到每个选项阶段 继承（Hit-to-Lead 的开始和 Lead Optimization 的开始）从此合同生成的数据。 将由 NINDS、贡献者或资助的研究人员用于支持研究性新药 （IND）申请指导的临床前活动的结果将成为本合同的基础。 临床前候选化合物正在进行进一步开发，即高级 PK 和毒理学 IND 申请准备过程中的评估。 NIH 通过该合同服务的项目和各个项目的最终目标是带来新的 为此，美国国立卫生研究院 (NIH) 已获得特殊情况决定权。 (DEC) 将卫生与公共服务部采购法规 (HHSAR) 纳入其中 第 352.227-11 条“专利权-特殊情况”和第 352.227-14 条“数据权利”中的条款 – 特殊情况，作为本次招标产生的任何合同的一部分。 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 治疗开发药物化学支持计划 (MCSP)。