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 离子通道是整体膜蛋白，可控制离子通过细胞膜的通量，它们 通常对电压和配体响应，导致活动/开放状态或不活跃/封闭状态。 此外，离子通道几乎涉及所有生理过程，包括细胞 - 细胞通信， 肌肉收缩，神经元发射，渗透应激反应等，这些蛋白质的功能障碍已是 与几种人类疾病有关，例如哮喘，高血压，糖尿病，一些癌症和先天性心脏 失败，列举一些例子。由于它们在疾病中的重要作用和作为药物靶标的潜力 对于表征离子通道反应的表征，尤其是在药物相互作用方面，这是一种极大的兴趣。 但是，关于开发针对目标特异性药物的能力仍然存在非常紧迫的问题 调节其他（非目标）离子通道的活性。这个过程非常困难，因为大多数离子渠道 有可能结合药物样分子的潜力。在此程序中，电子生物科学， Inc.（EB）将开发并演示一个自动化的，多重的，基于流体的系统，该系统将允许多个 与最先进的噪声/分辨率同时筛选的离子通道和药物目标 在单通道级别。诸如此处提出的工具，能够广泛，高通量广告 药物筛查（即许多离子通道和许多药物）将有助于扩大所需的信息池 设计和表征新的高亲和力/高特异性药物，以改善患者护理。