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).

国家神经疾病和中风研究所(NINDS)和美国国立卫生研究院的蓝图 神经治疗网络(BPN)http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm有需求 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 发展构效关系(SAR)分析和设计、合成、体外吸收、 分布、新陈代谢、排泄和毒理学(ADMET)、计算化学/计算机辅助 药物发现(CADD)和储存和运输的复合物流，以支持贡献者 Mouradian/Disney(罗格斯/斯克里普斯)开发一种新的治疗帕金森症的有效方法。这将是 通过提高它们的小分子杂环起始化合物的SAR/SPR来实现 检测和体外ADMET，以确定新的，选择性的靶酶抑制剂 我们的药物发现方法将是合成基于杂环的新型配体。 具有很强抑制作用的支架。候选分子将接受分析以评估标准 特别与化合物在治疗环境中的物理化学性质有关，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。这个 目标是将项目推进到进行/不进行决策，并进行到 继任(开始点击到销售线索和开始销售线索优化)。从该合同生成的数据 将由NINDS、贡献者或受赞助的调查人员用于支持研究新药 (IND)应用指导临床前活动。这份合同的努力成果将是 用于进一步开发的高级临床前候选化合物，即高级PK和毒理学 对IND备案文件的准备进行评估。 本合同所服务的NIH项目和单个项目的最终目标是带来新的 药品上市。为此，美国国家卫生研究院被授予了例外情况的决定。 (12月)纳入卫生与公众服务部采购规例(HHSAR) 352.227-11条，专利权--例外情况和352.227-14条，数据权利-- 特殊情况，作为本次招标所产生的任何合同的一部分。香港特别行政区的条款 将使贡献者能够保持对通过以下方式产生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)。