
Discovery of Potent and Selective MNK Kinase Inhibitors for the ...
2025年3月4日 · MNK activity is regulated by the p38 and Erk MAPK pathways. Phosphorylation of MNK leads to its activation and binding to the eIF4G/eIF4E complex. MNK then phosphorylates eIF4E at Ser209, whose activation is associated with oncogene translation, leading to tumorigenesis. Given this important role for eIF4E in tumorigenesis, MNK inhibition with novel small molecule inhibitors could be a ...
MNK, mTOR or eIF4E-selecting the best anti-tumor target for …
2023年11月15日 · 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.
MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven
2014年11月18日 · We propose that MNKs can modulate oncogenic translation by regulating eIF4E1-eIF4E3 levels and activity in DLBCL. There are multiple aetiologies to cancer development and maintenance, which...
The MNK-1/eIF4E pathway as a new therapeutic pathway to …
Here we present data that inhibition of MAPK-activated protein kinase (MNK)-1 reduces inflammation and remodelling. MNK-1 regulates protein expression by controlling mRNA stability, nuclear export and translation through the eukaryotic initiation factor 4E (eIF4E). Airway smooth muscle cells were derived from asthmatic and non-asthmatic donors.
MNK、mTOR 或 eIF4E——选择阻断翻译起始的最佳抗肿瘤靶 …
为了探索 MNK、mTOR 和 eIF4E 之间的最佳抗癌靶点,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点抑制剂的结构和活性。 通过分析抑制剂的不同特性,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 相互作用可能是靶向翻译起始的最有前途的抗癌方法。 eIF4E 过度表达在各种实体瘤和血液癌症患者中很常见。 eIF4E作为潜在的抗癌靶点,引起了研究人员的广泛关注 …
Mnk earmarks eIF4E for cancer therapy - PMC
The phosphorylation of eIF4E by Mnk1/2 provides a new avenue for cancer therapy. The inhibition of eIF4E phosphorylation could have similar consequences as the inhibition mTORC1 by rapalaogs, but with the advantage that it does not elicit the activation of Akt as a result of the inhibition of the negative feedback loops mediated by mTORC1.
MNK-driven eIF4E phosphorylation regulates the fibrogenic ...
2024年8月15日 · We delineate a unique JNK/MNK/eIF4E signaling axis in fibrotic MCs with an interesting and surprising finding that JNK is the primary kinase upstream of constitutively increased phosphorylation of eIF4E in these cells derived …
9HRC: Structure of MNK2 in complex with inhibitor NUCC …
2024年12月17日 · MNK then phosphorylates eIF4E at Ser209, whose activation is associated with oncogene translation, leading to tumorigenesis. Given this important role for eIF4E in tumorigenesis, MNK inhibition with novel small molecule inhibitors could be a promising strategy to combat AML, which continues to be an area of unmet medical need. ...
The Akt/mTOR and MNK/eIF4E pathways rewire the prostate …
Among different secreted proteins released by prostate tumor cells, we identified Hgf, Spp1, and Bgn as the key factors that regulate MDSCs migration. Mechanistically, we found that the coordinated loss of Pdcd4 and activation of the MNK/eIF4E pathways regulate the mRNAs translation of Hgf, Spp1 and Bgn. MDSCs infiltration and tumor growth were ...
Targeting translation: eIF4E as an emerging anticancer drug target
2016年1月18日 · Mnk-induced eIF4E phosphorylation is closely related to mTOR pathway inhibition (Refs Reference Shi 145, Reference Wang 146). Two research groups have proposed a new strategy of enhancing mTOR-targeted cancer …