4.7 Article

New Protocol-Guided Exploitation of a Lysosomal Sulfatase Inhibitor to Suppress Cell Growth in Glioblastoma Multiforme

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JOURNAL OF MEDICINAL CHEMISTRY
卷 64, 期 12, 页码 8599-8606

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AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.1c00559

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  1. National Natural Science Foundation of China [2183309, 21673237]

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The study found that lysosomal sulfatase expression is closely related to the prognosis of glioblastoma. A new probe, MNG, was developed to detect lysosomal sulfatase, and the first reported lysosomal sulfatase inhibitor, sulbactam, was found to inhibit tumor growth in GBM.
Glioblastoma multiforme (GBM) is a highly invasive and aggressive malignant glioma. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma, so more effective strategies of antitumor treatments are in urgent demand. Here, we found that lysosomal sulfatase expression was significantly correlated with poor prognosis of GBM. Hence, a new probe, MNG, was developed with a new protocol utilizing glucose groups to detect lysosomal sulfatase. It also exhibits potential for monitoring GBM cells, depending on the hyperactive lysosomal sulfatase expression of tumor cells. Meantime, we identified that sulbactam as the first reported lysosomal sulfatase inhibitor inhibits the tumor growth of GBM. Collectively, our work highlights that lysosomal sulfatase was detected using a new protocol and its potential as a therapeutic target in GBM and reveals a distinct mechanism that sulbactam inhibits cell proliferation related to lysosomal sulfatase, indicating that sulbactam could be a promising therapeutic agent against GBM.

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