AIM The aim of the present study was to discover novel protein tyrosine phosphatase 1B (PTP1B) inhibitors. We expressed and purified the human PTP1B catalytic domain and set up a molecular level high-throughput screening (HTS) assay to screen a set of 48,000 pure compounds. RESULTS HTS was finished with an averaged Zo factor of 0.63, and LGH00081, a competitive inhibitor of PTP1B with novel structure and relatively good selectivity for receptor-type protein tyrosine phosphatases, was identified. CONCLUSION We established a molecular level assay which is useful for the screening of PTP1B inhibitors with therapeutic potential. The novel competitive PTP1B inhibitor LGH00081 offers a good start for structure modification and cellular functional activity study.

中文翻译：

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通过高通量筛选发现一种新型竞争性PTP1B抑制剂。

目的本研究的目的是发现新型的蛋白酪氨酸磷酸酶1B（PTP1B）抑制剂。我们表达并纯化了人PTP1B催化结构域，并建立了分子水平的高通量筛选（HTS）分析方法，以筛选一组48,000个纯化合物。结果HTS的平均Zo因子为0.63，并鉴定了LGH00081，它是PTP1B的竞争性抑制剂，具有新颖的结构和对受体型酪氨酸磷酸酶的相对较好的选择性。结论我们建立了一种分子水平测定方法，可用于筛选具有治疗潜力的PTP1B抑制剂。新型竞争性PTP1B抑制剂LGH00081为结构修饰和细胞功能活性研究提供了良好的开端。