High-throughput, Multiplexed, Commercialized Ion Channel Drug Screening

高通量、多重、商业化离子通道药物筛选

• 批准号: 10080356
• 负责人: Anna Schibel
• 金额: $ 22.45万
• 依托单位: ELECTRONIC BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080356
• 关键词: Achievement; Address; Affinity; Amplifiers; Asthma; Binding; Biological Sciences; Cell Communication; Cell Wall; Cell physiology; Cells; Cellular Membrane; Chemicals; Cyclodextrins; Detection; Development; Devices; Diabetes Mellitus; Disease; Drug Interactions; Drug Prescriptions; Drug Screening; Drug Targeting; Electronics; Engineering; Ensure; Evaluation; Event; Functional disorder; Genome; Healthcare; Heart failure; Hemolysin; Hypertension; Individual; Integral Membrane Protein; Investigation; Ion Channel; Ion Channel Protein; Ions; Kinetics; Ligands; Lipid Bilayers; Liquid substance; Malignant Neoplasms; Marketing; Measurement; Membrane; Membrane Lipids; Methods; Microfluidics; Molecular Conformation; Monitor; Muscle Contraction; Names; Neurons; Noise; Patient Care; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physiological Processes; Procedures; Process; Proteins; Research; Resolution; Risk; Role; Safety; Signal Transduction; Specificity; System; Systems Development; Systems Integration; Technology; Temperature; Testing; Therapeutic; Time; Work; aerolysin; base; biological adaptation to stress; cost; design; drug development; human disease; improved; inhibitor/antagonist; interest; mutant; nanopore; novel therapeutics; parallelization; patch clamp; patient safety; prevent; programs; quality assurance; reconstitution; research and development; response; screening; sensor; sensor technology; small molecule; solid state; technology development; temporal measurement; tool; voltage

Project Summary Ion channels are integral membrane proteins that control the flux of ions through cellular membranes and they are often responsive to voltages and ligands, resulting in an active/open state or inactive/closed state. Furthermore, ion channels are involved nearly all physiological processes, including cell-cell communication, muscle contraction, neuronal firing, osmotic stress responses, etc., and dysfunction of these proteins has been related to several human diseases such as asthma, hypertension, diabetes, some cancers, and congenital heart failure, to name a few examples. Because of their important role in disease and potential as drug targets, there is a great deal of interest in characterizing ion channel response, especially regarding drug interactions. However, there remain very pressing issues regarding the ability to develop target-specific drugs that do not modulate the activity of other (non-target) ion channels. This process is quite difficult as most ion channels that have the potential to bind drug-like molecules remain understudied. During this program, Electronic BioSciences, Inc. (EBS) will develop and demonstrate an automated, multiplexed, fluidic-based system that will allow multiple ion channels and drug targets to be screened simultaneously with state-of-the-art noise-performance/resolution at the single-channel level. A tool such as the one proposed here, capable of broad, high-throughput commercial drug screening (i.e., many ion channels and many drugs), will help expand the pool of information needed to design and characterize new high-affinity/high-specificity drugs for improved patient care.

项目摘要 离子通道是一种膜蛋白，它控制着细胞膜上的离子流， 通常响应于电压和配体，导致活性/开放状态或非活性/闭合状态。 此外，离子通道参与几乎所有的生理过程，包括细胞-细胞通讯， 肌肉收缩、神经元放电、渗透应激反应等，这些蛋白质的功能障碍 与几种人类疾病有关，如哮喘、高血压、糖尿病、某些癌症和先天性心脏病 失败，举几个例子。由于它们在疾病中的重要作用和作为药物靶点的潜力， 在表征离子通道反应方面引起了人们的极大兴趣，尤其是在药物相互作用方面。 然而，关于开发不具有靶向特异性的药物的能力，仍然存在非常紧迫的问题。 调节其它（非靶）离子通道的活性。这个过程是相当困难的，因为大多数离子通道， 是否具有结合药物样分子的潜力仍未得到充分研究。在这个项目中，电子生物科学， Inc. (EBS)将开发和演示一个自动化的，多路复用的，基于流体的系统，将允许多个 离子通道和药物靶点可同时进行筛选，具有最先进的噪声性能/分辨率 在单通道水平上。一个工具，如一个在这里提出的，能够广泛的，高通量的商业 药物筛选（即，许多离子通道和许多药物），将有助于扩大所需的信息库， 设计和表征新的高亲和力/高特异性药物，以改善患者护理。