{"title":"MAP4K3/GLK：结构、分子药理学和药物开发。","authors":"Jingwen Wang, Xiaoe Yan, Haibo Li, Yudao Shen, Caihong Yun, Jianming Zhang","doi":"10.1016/j.bioorg.2025.109043","DOIUrl":null,"url":null,"abstract":"<p><p>GLK (also known as MAP4K3), classified as a member of the MAP4K family, is a Ste20-like serine/threonine kinase. GLK plays a pivotal role in multiple cellular signaling pathways, including TCR-mediated immune responses, as well as the JNK, mTOR, and NF-κB signaling pathways. Due to its critical role in these key regulatory networks, GLK has been implicated in the pathogenesis of various diseases, including autoimmune diseases, cancer, aging, and COVID-19 infection. Consequently, GLK represents a promising molecular target for the development of novel therapeutic interventions for immunotherapy and oncotherapy. This review comprehensively summarizes the signaling pathways and human diseases regulated by GLK, focusing on GLK protein kinase structure, GLK-specific regulators, and profiling strategies for developing GLK-specific small-molecule inhibitors.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"109043"},"PeriodicalIF":4.7000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"MAP4K3/GLK: Structure, molecular pharmacology and drug development.\",\"authors\":\"Jingwen Wang, Xiaoe Yan, Haibo Li, Yudao Shen, Caihong Yun, Jianming Zhang\",\"doi\":\"10.1016/j.bioorg.2025.109043\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>GLK (also known as MAP4K3), classified as a member of the MAP4K family, is a Ste20-like serine/threonine kinase. GLK plays a pivotal role in multiple cellular signaling pathways, including TCR-mediated immune responses, as well as the JNK, mTOR, and NF-κB signaling pathways. Due to its critical role in these key regulatory networks, GLK has been implicated in the pathogenesis of various diseases, including autoimmune diseases, cancer, aging, and COVID-19 infection. Consequently, GLK represents a promising molecular target for the development of novel therapeutic interventions for immunotherapy and oncotherapy. This review comprehensively summarizes the signaling pathways and human diseases regulated by GLK, focusing on GLK protein kinase structure, GLK-specific regulators, and profiling strategies for developing GLK-specific small-molecule inhibitors.</p>\",\"PeriodicalId\":257,\"journal\":{\"name\":\"Bioorganic Chemistry\",\"volume\":\"165 \",\"pages\":\"109043\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1016/j.bioorg.2025.109043\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/j.bioorg.2025.109043","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
MAP4K3/GLK: Structure, molecular pharmacology and drug development.
GLK (also known as MAP4K3), classified as a member of the MAP4K family, is a Ste20-like serine/threonine kinase. GLK plays a pivotal role in multiple cellular signaling pathways, including TCR-mediated immune responses, as well as the JNK, mTOR, and NF-κB signaling pathways. Due to its critical role in these key regulatory networks, GLK has been implicated in the pathogenesis of various diseases, including autoimmune diseases, cancer, aging, and COVID-19 infection. Consequently, GLK represents a promising molecular target for the development of novel therapeutic interventions for immunotherapy and oncotherapy. This review comprehensively summarizes the signaling pathways and human diseases regulated by GLK, focusing on GLK protein kinase structure, GLK-specific regulators, and profiling strategies for developing GLK-specific small-molecule inhibitors.
期刊介绍：
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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