BD2K product for enhancing phenotypic screens

用于增强表型筛选的 BD2K 产品

• 批准号: 10020785
• 负责人: Jennifer Fuller
• 金额: $ 72.98万
• 依托单位: GENECENTRIX, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10020785
• 关键词: Address; Adverse event; Agonist; Algorithms; Antipsychotic Agents; Area; Atlases; Award; Big Data; Big Data to Knowledge; Bioinformatics; Biological Assay; Biological Models; Brain; Buprenorphine; Bupropion; Businesses; Cell Nucleus; Cells; Clinic; Clinical; Clozapine; Clozaril; Computational Biology; Computer software; Data; Data Set; Development; Disease; Drug Addiction; Drug Antagonism; Drug Industry; Drug Kinetics; Drug Screening; Epidemic; Funding; Gene Expression; Goals; Informatics; Investments; Lead; Licensing; Market Research; Mental Health; Methadone; Methods; Modeling; Molecular; Molecular Computations; Molecular Target; Naltrexone; National Institute of Drug Abuse; Neurosciences; Nucleus Accumbens; Pattern; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Phenotype; Probability; Process; Proteomics; Psychiatry; Public Health; Publications; Reporting; Research; Side; Sister; Specificity; Spinal Ganglia; Statistical Models; Structure; Substance abuse problem; Technology; Testing; Time; Tissues; Translating; Translations; United States National Institutes of Health; Update; addiction; base; brain tissue; cloud based; commercialization; computational chemistry; craving; data harmonization; data integration; design; digital; drug action; drug candidate; drug development; drug discovery; drug of abuse; falls; human tissue; insight; interest; molecular modeling; mu opioid receptors; novel; novel drug class; novel therapeutics; opioid use disorder; prescription opioid; prevent; product development; programs; protein expression; prototype; receptor; research and development; screening; screening program; small molecule; tool; trend; user-friendly; validation studies

The public health problem addressed by the proposed project is the critical, long-term absence of progress in anti-addiction medication discovery and development. GeneCentrix’ “historeceptomics” technology has the potential to alter this trend by providing advanced insights during the process of anti-addiction medication discovery and development. Digital/computational advanced insights are recognized as the critical value- added emerging piece of technology in pharmaceutical R&D. The unique concept underlying our technology is specificity of anti-addiction drug action in different brain tissues. No software product currently provides this capability. The overall goal of this program is to commercialize a product that enhances anti-addiction medication discovery by providing previously unavailable advanced structure-activity insights specifically targeted to phenotypic screening assays. A Phase I award successfully established the technical merit, feasibility and commercial potential of the envisioned product, as well as identifying the key remaining concerns of customers who expressed intent to purchase the product capabilities. The overall objective of this Phase II renewal is to produce a commercialization ready software product that eliminates the remaining concerns of the customers for commercialization. Based on the prototype built in Phase I and the insights gained from market analysis, the remaining obstacles to commercialization and sustainability of the product have been identified. In this Phase II project, we will establish a partnership with a sister company in the space, Molsoft LLC, whose products already addresses a key customer concern. The GeneCentrix technology to enhance the translatability of phenotypic screens will be integrated as feature into Molsoft’s ICM product line (Aim 1). In addition, customer requested and sponsor (NIDA/NCATS)-desired R&D will update the product core to optimize it for anti-addiction drug discovery by incorporation of new and growing brain atlas, proteomic and pharmacokinetic big data (Aim 2). For this FOA, this application falls within Area 4: Tools and Model Systems for OUD Research and proposes a project including the development of drug discovery and development- enabling technologies. Funding is sought for activities and steps in the product development process encompassing the development and demonstration of the capability of bioinformatic methods or algorithms for research data integration and data harmonization. Accordingly, as required by the FOA, a broad validation study (Aim 3) will be performed of the technology that that will demonstrate and validate the commercial utility and value proposition of the proposed technology. The commercial plan establishes a clear and feasible approach to take advantage of a growing business opportunity that should lead to a sustainable product cycle with minimal further Phase III investment. Overall, a needed commercial software product could emerge from NIH product development support that could contribute to anti-addiction drug discovery.

拟议项目所解决的公共卫生问题是， 抗成瘾药物的发现和开发。GeneCentrix的“组织感受器”技术 有可能通过在抗成瘾药物治疗过程中提供先进的见解来改变这一趋势 发现和发展。数字/计算高级洞察力被公认为关键价值- 增加了制药研发的新兴技术。我们的技术背后的独特概念是 不同脑组织中抗成瘾药物作用的特异性。目前没有软件产品提供 这种能力。这个计划的总体目标是将一种增强抗成瘾性的产品商业化 通过提供以前无法获得的高级结构-活性洞察， 靶向于表型筛选测定。第一阶段奖项成功确立了技术优势， 设想产品的可行性和商业潜力，以及确定关键的剩余 表示有意购买产品功能的客户的关注。本报告的总体目标 第二阶段的更新是生产一个商业化的软件产品，消除剩余的 客户对商业化的关注。基于第一阶段建立的原型和 从市场分析中得出的结论，产品商业化和可持续性的剩余障碍 已被确认。在这个二期项目中，我们将与该领域的一家姐妹公司建立合作关系， Molsoft LLC，其产品已经解决了一个关键的客户问题。GeneCentrix技术 增强表型筛选的可翻译性将作为功能集成到Molsoft的ICM产品线中 (Aim 1）。此外，客户要求和赞助商（NIDA/NCATS）期望的研发将更新产品核心 通过整合新的和不断增长的大脑图谱，蛋白质组学和 药代动力学大数据（Aim 2）。对于此FOA，此应用程序福尔斯属于区域4：工具和模型系统 为OUD研究，并提出了一个项目，包括药物发现和开发的发展- 使能技术。为产品开发过程中的活动和步骤寻求资金 包括生物信息学方法或算法的能力的开发和演示， 研究数据整合和数据协调。因此，根据FOA的要求， 将对技术进行研究（目标3），以证明和验证商业实用性 和价值主张。商业计划书建立了一个清晰可行的 利用不断增长的商业机会，实现可持续的产品周期 第三阶段投资最少。总的来说，一个所需的商业软件产品可能会出现在 NIH产品开发支持，可能有助于抗成瘾药物的发现。

项目成果

How polypharmacologic is each chemogenomics library?

每个化学基因组库的多药理学如何？

• DOI: 10.4155/fdd-2019-0032
• 发表时间: 2020
• 期刊: Future drug discovery
• 作者: Ni,Eric;Kwon,Eehjoe;Young,LaurenM;Felsovalyi,Klara;Fuller,Jennifer;Cardozo,Timothy
• 通讯作者: Cardozo,Timothy