Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Molecules. 2020 Dec 23;26(1):33. doi: 10.3390/molecules26010033.
-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 was finally identified as the best candidate. Further experiments confirmed that compound inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line. Results further suggest that compound could promote the expression of E-cadherin by targeting CD147, thereby inhibiting tumor migration. Finally, the structures of the other potential CD147 -glycosylation inhibitors may eventually provide guidance for future optimization.
糖基化对于 CD147 功能的调节至关重要，包括 CD147 的成熟、基质金属蛋白酶（MMPs）的分泌以及肿瘤转移的促进。糖基化的 CD147 在各种癌症类型中高表达，参与转移，并与恶性肿瘤的不良预后相关。然而，迄今为止，针对 CD147 糖基化的特异性靶点抑制剂的开发很少。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实验发现 CD147 糖基化抑制剂的策略。筛选出四种化合物作为潜在的 CD147 糖基化抑制剂。其中，化合物 被最终确定为最佳候选物。进一步的实验证实，化合物 抑制了 Hela 细胞系中 MMPs 的产生和癌细胞的转移。结果进一步表明，化合物 通过靶向 CD147 可促进 E-钙黏蛋白的表达，从而抑制肿瘤迁移。最后，其他潜在的 CD147-糖基化抑制剂的结构可能最终为未来的优化提供指导。
