High-throughput, Multiplexed, Commercialized Ion Channel Drug Screening

项目摘要 离子通道是控制离子通过细胞膜的流量的完整的膜蛋白，它们 通常对电压和配体作出响应，导致活动/开放状态或非活动/闭合状态。 此外，离子通道几乎涉及所有的生理过程，包括细胞间的通讯， 肌肉收缩、神经元放电、渗透应激反应等，以及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，仅举几个例子。由于它们在疾病中的重要作用和潜在的药物靶标， 对于表征离子通道的反应，特别是关于药物的相互作用，人们非常感兴趣。 然而，在开发不起作用的靶向药物的能力方面仍然存在非常紧迫的问题。 调节其他(非靶标)离子通道的活性。这一过程相当困难，因为大多数离子通道 是否具有结合类药物分子的潜力仍未得到充分研究。在这个节目中，电子生物科学， 公司(EBS)将开发和演示一种自动化、多路复用、基于流体的系统，该系统将允许 离子通道和药物靶标将与最先进的噪声同时进行筛选-性能/分辨率 在单通道级别。像这里建议的这样的工具，能够广泛、高吞吐量地进行商业 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。

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.