State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, Shandong, PR China.
Eur J Med Chem. 2023 Nov 15;260:115781. doi: 10.1016/j.ejmech.2023.115781. Epub 2023 Sep 1.
Overexpression of eIF4E is common in patients with various solid tumors and hematologic cancers. As a potential anti-cancer target, eIF4E has attracted extensive attention from researchers. At the same time, mTOR kinases inhibitors and MNK kinases inhibitors, which are directly related to regulation of eIF4E, have been rapidly developed. To explore the optimal anti-cancer targets among MNK, mTOR, and eIF4E, this review provides a detailed classification and description of the anti-cancer activities of promising compounds. In addition, the structures and activities of some dual-target inhibitors are briefly described. By analyzing the different characteristics of the inhibitors, it can be concluded that MNK1/2 and eIF4E/eIF4G interaction inhibitors are superior to mTOR inhibitors. Simultaneous inhibition of MNK and eIF4E/eIF4G interaction may be the most promising anti-cancer method for targeting translation initiation.
eIF4E 的过表达常见于各种实体瘤和血液系统恶性肿瘤患者中。作为一种潜在的抗癌靶点，eIF4E 引起了研究人员的广泛关注。同时，与 eIF4E 调节直接相关的 mTOR 激酶抑制剂和 MNK 激酶抑制剂也得到了快速发展。为了在 MNK、mTOR 和 eIF4E 中探索最佳抗癌靶点，本综述对有前景的化合物的抗癌活性进行了详细的分类和描述。此外，还简要描述了一些双靶抑制剂的结构和活性。通过分析抑制剂的不同特点，可以得出结论：MNK1/2 和 eIF4E/eIF4G 相互作用抑制剂优于 mTOR 抑制剂。同时抑制 MNK 和 eIF4E/eIF4G 相互作用可能是针对翻译起始的最有前途的抗癌方法。
