Dodgson K, Gedge L, Murray D C, Coldwell M
Bioscience Department, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, UK.
J Recept Signal Transduct Res. 2009;29(3-4):163-72. doi: 10.1080/10799890903079844.
Seven-transmembrane receptors (7TMRs) are a family of proteins of great interest as therapeutic targets because of their abundance on the cell surface, diverse effects in modulating cell behavior and success as a key class of drugs. We have evaluated the Epic label-free system for the purpose of identifying antagonists of the muscarinic M3 receptor. We compared the data generated from the label-free technology with data for the same compounds in a calcium flux assay. We have shown that this technology can be used for high throughput screening (HTS) of 7TMRs and as an orthogonal approach to enable rapid evaluation of HTS outputs. A number of compounds have been identified which were not found in a functional HTS measuring the output from a single pathway, which may offer new approaches to inhibiting responses through this receptor.
七跨膜受体（7TMRs）是一类备受关注的蛋白质家族，因其在细胞表面大量存在，在调节细胞行为方面具有多种作用，并且作为一类关键药物取得了成功，所以成为极具吸引力的治疗靶点。我们评估了Epic无标记系统，目的是鉴定毒蕈碱M3受体的拮抗剂。我们将无标记技术产生的数据与同一化合物在钙流测定中的数据进行了比较。我们已经表明，该技术可用于7TMRs的高通量筛选（HTS），并作为一种正交方法，以便快速评估HTS输出结果。已经鉴定出一些在测量单一信号通路输出的功能性HTS中未发现的化合物，这可能为通过该受体抑制反应提供新方法。
