Abstract
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 Z′ 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.
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Project supported by National Natural Science Foundation of China grants (No 30623008, 30200341, and 30400560) and a Shanghai Commission of Science and Technology grant (No 054319910).
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Shi, L., Yu, Hp., Zhou, Yy. et al. Discovery of a novel competitive inhibitor of PTP1B by high-throughput screening. Acta Pharmacol Sin 29, 278–284 (2008). https://doi.org/10.1111/j.1745-7254.2008.00737.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00737.x
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