Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
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CD147 N-聚糖抑制剂的发现和生物学评价：治疗肿瘤转移的新方向
DOI：
10.3390/molecules26010033
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发表时间：
2020-12-23
期刊：
影响因子：
--
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Li W;Wang D;Ge Y;Zhang L;Wu J;Liu D
N-糖基化对CD 147功能的调节起重要作用，包括CD 147的成熟、基质金属蛋白酶（MMPs）的分泌以及促进肿瘤转移。糖基化CD 147在多种癌症类型中高度表达，参与转移，并且与恶性肿瘤的不良预后相关。然而，迄今为止，几乎没有开发针对CD 147糖基化的靶向特异性抑制剂。在这项工作中，我们报告了一种通过计算机辅助筛选和抑制试验发现CD 147糖基化抑制剂的策略。筛选出4个化合物作为潜在的CD 147糖基化抑制剂。其中，化合物72最终被确定为最佳候选物。进一步的实验证实，化合物72抑制Hela细胞系中MMP的产生和癌细胞的转移。结果进一步表明，化合物72可以通过靶向CD 147促进E-钙粘蛋白的表达，从而抑制肿瘤迁移。最后，其他潜在的CD 147 N-糖基化抑制剂的结构可能最终为未来的优化提供指导。
N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis. Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors. However, to date, there has been little development of target-specific inhibitors for CD147 glycosylation. In this work, we report a strategy for discovering CD147 glycosylation inhibitors through computer-aided screening and inhibition assays. Four compounds were screened as potential CD147 glycosylation inhibitors. Of these, compound 72 was finally identified as the best candidate. Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line. Results further suggest that compound 72 could promote the expression of E-cadherin by targeting CD147, thereby inhibiting tumor migration. Finally, the structures of the other potential CD147 N-glycosylation inhibitors may eventually provide guidance for future optimization.
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