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丝裂原活化蛋白激酶相互作用激酶抑制剂在肿瘤免疫治疗中的研究进展

Research progress of mitogen-activated protein kinase interacting kinases inhibitors in tumor immunotherapy

  • 摘要: 随着肿瘤免疫疗法(tumor immunotherapy)的兴起,靶向免疫系统的小分子调节剂已成为研究热点,而免疫激酶作为一类研究较深入发展较成熟的靶点,受到越来越多的关注。丝裂原活化蛋白激酶(MAPK)相互作用激酶(MNKs)位于ERK和p38 MAPK信号通路的交汇点,可以在保守的丝氨酸209处特异性磷酸化真核翻译起始因子4E(eIF4E)并调节mRNA的翻译。MNKs信号通路在先天性和适应性免疫系统中起着重要作用,MNKs抑制剂在治疗肿瘤及免疫相关疾病的研究也越来越深入。本文就MNKs的结构特点、作用机制、信号转导途径及其与肿瘤的密切关系进行了总结,同时详细介绍了不同研究机构报道的 MNKs抑制剂的发展过程和临床研究进展。

     

    Abstract: With the rise of tumor immunotherapy, small molecule modulators targeting the immune system have become a research hotspot. As well-developed and mature targets, immunity protein kinases have attracted more and more attention. Mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are located at the meeting-point of ERK and p38 MAPK signaling pathways, which can phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at the conserved serine 209 exclusively and modulate the translation of mRNA. Herein we review the structural characteristics, mechanism, signaling transduction pathways and close relationship with tumors of MNKs.Meanwhile, the development process and clinical research progress of the MNKs inhibitors reported by different research institutions are introduced in detail.

     

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