首页> 外文期刊>Life sciences >MONOCLONAL ANTIBODIES AS SURROGATE RECEPTORS IN A HIGH THROUGHPUT SCREEN FOR COMPOUNDS THAT ENHANCE INSULIN SENSITIVITY
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MONOCLONAL ANTIBODIES AS SURROGATE RECEPTORS IN A HIGH THROUGHPUT SCREEN FOR COMPOUNDS THAT ENHANCE INSULIN SENSITIVITY

机译:单克隆抗体在高通量屏幕中作为替代受体,用于增强胰岛素敏感性的化合物

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Monoclonal antibodies (MoAbs) were made to a known insulin sensitivity enhancer (ISE) compound, CS-045. The MoAbs were characterized with respect to binding other known thiazolidinedione ISE compounds using a CS-045 labeled with b-phycoerythrin in a competitive particle concentration fluorescence immunoassay (PCFIA). By comparing the rank order of IC50 values for each compound to its respective potency as an ISE, one MoAb (13E3) was selected for further characterization. This MoAb was also used as a surrogate receptor in a high throughput screen to identify novel compounds that compete for binding to CS-045. Some of the hits were found to have efficacy in reducing blood glucose. Subsequently, another group reported that several compounds with the core thiazolidinedione structure of the ISE compounds bound with high affinity to peroxisome proliferator-activating receptors (PPAR). Therefore, we used the MoAb assay to test these and other compounds that are known to bind to PPAR gamma and noted crossreactivity with some of the compounds. [References: 30]
机译:制备了针对已知胰岛素敏感性增强剂(ISE)化合物CS-045的单克隆抗体(MoAb)。在竞争性颗粒浓度荧光免疫分析(PCFIA)中,使用b-藻红蛋白标记的CS-045,对MoAb结合其他已知的噻唑烷二酮ISE化合物进行了表征。通过将每种化合物的IC50值的排名顺序与其作为ISE的效价进行比较,选择了一种MoAb(13E3)进行进一步表征。在高通量筛选中,该MoAb还用作替代受体,以鉴定竞争与CS-045结合的新型化合物。发现某些命中具有降低血糖的功效。随后,另一小组报告说,具有ISE化合物噻唑烷二酮核心结构的几种化合物与过氧化物酶体增殖物激活受体(PPAR)具有高亲和力。因此,我们使用MoAb分析法测试了这些和其他已知与PPARγ结合的化合物,并指出了与某些化合物的交叉反应性。 [参考:30]

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