Determination of half-maximal inhibitory concentration using biosensor-based protein interaction analysis.
Determination of half-maximal inhibitory concentration using biosensor-based protein interaction analysis.
复制标题
DOI：
10.1016/j.ab.2016.06.025
复制
发表时间：
2016-09-01
影响因子：
2.9
通讯作者：
Martinez-Hackert E
中科院分区：
文献类型：
--
作者：
Aykul S;Martinez-Hackert E
半数最大抑制浓度（IC 50）是最广泛使用的药物功效的信息测量。它表明需要多少药物才能将生物过程抑制一半，从而提供了药理学研究中拮抗剂药物效力的测量。大多数确定药理学化合物的IC 50的方法是基于利用全细胞系统的测定。虽然它们通常提供突出的效力信息，但结果可能取决于所使用的实验细胞系，并且可能无法区分化合物抑制特定相互作用的能力。在这里，我们显示使用分泌的转化生长因子-β（TGF-β）家族配体BMP-4及其受体作为示例，表面等离子体共振可以用于准确地确定单个配体-受体配对的IC 50值。用这种方法实现的分子分辨率可以帮助区分特异性靶向单个复合物的抑制剂，或者可以同时抑制多种功能相互作用的抑制剂。
The half-maximal inhibitory concentration (IC50) is the most widely used and informative measure of a drug’s efficacy. It indicates how much drug is needed to inhibit a biological process by half, thus providing a measure of potency of an antagonist drug in pharmacological research. Most approaches to determine IC50 of a pharmacological compound are based on assays that utilize whole cell systems. While they generally provide outstanding potency information, results can depend on the experimental cell line used and may not differentiate a compound’s ability to inhibit specific interactions. Here we show using the secreted Transforming Growth Factor-β (TGF-β) family ligand BMP-4 and its receptors as example that surface plasmon resonance can be used to accurately determine IC50 values of individual ligand-receptor pairings. The molecular resolution achievable with this approach can help distinguish inhibitors that specifically target individual complexes, or that can inhibit multiple functional interactions at the same time.