摘要
雷帕霉素的机制/哺乳动物靶点(mTOR)是调节细胞生命周期中关键步骤的信号通路的关键枢纽。一旦加入mTORC1复合物,mTOR就会磷酸化真核起始因子4E(eIF4E)结合蛋白1(4E-BP1),然后释放eIF4E。当不与4个ebp结合时,eIF4E识别mRNA5‘-cap结构,并与eIF4A和eIF4G一起形成eIF4F复合物,招募mRNA上的核糖体。在正常情况下,eIF4E的细胞浓度很低,这使得eIF4E成为蛋白质合成起始的限制因子。绝大多数癌症类型的特征是同时mTOR/4E-BP1信号通路解除和eIF4E上调,导致促癌促进基因的表达增加和细胞生长解除。在过去的几十年里,越来越多的mTOR/4E-BP1/eIF4E通路的选择性抑制剂被发现或设计出来。几种令人鼓舞的临床前结果的抑制剂已经在临床试验中进行了测试。本文综述了针对mTOR、4E-BP1和eIF4E的药物开发的最新研究,描述了最有前途的化合物的设计原理和可用的结构和功能数据。
关键词: mTOR变构抑制剂,雷帕霉素,eIF4F,转译控制,癌症,PIKKs。
Current Medicinal Chemistry
Title:The mTOR/4E-BP1/eIF4E Signalling Pathway as a Source of Cancer Drug Targets
Volume: 29 Issue: 20
关键词: mTOR变构抑制剂,雷帕霉素,eIF4F,转译控制,癌症,PIKKs。
摘要: The mechanistic/mammalian target of rapamycin (mTOR) is the crucial hub of signalling pathways that regulate essential steps in the cell life cycle. Once incorporated in the mTORC1 complex, mTOR phosphorylates the eukaryotic initiation factor 4E (eIF4E)- binding protein 1 (4E-BP1), which then releases eIF4E. When not bound to 4EBPs, eIF4E recognizes the mRNA 5’-cap structure and, together with eIF4A and eIF4G, it forms the eIF4F complex that recruits the ribosome on the mRNA. Under normal conditions, the cellular concentration of eIF4E is very low, making eIF4E the limiting factor in the initiation of protein synthesis. The vast majority of cancer types are characterized by the simultaneous deregulation of the mTOR/4E-BP1 signalling pathway and upregulation of eIF4E, which lead to an increased expression of cancer-promoting genes and deregulated cellular growth. Over the last decades, a growing number of selective inhibitors of the mTOR/4E-BP1/eIF4E pathway have been discovered or designed. Several inhibitors with encouraging preclinical results have been tested in clinical trials. This review summarizes the most recent research on drug development against mTOR, 4E-BP1, and eIF4E, describing the design rationale and the available structural and functional data on the most promising compounds.
Export Options
About this article
Cite this article as:
The mTOR/4E-BP1/eIF4E Signalling Pathway as a Source of Cancer Drug Targets, Current Medicinal Chemistry 2022; 29 (20) . https://dx.doi.org/10.2174/0929867329666220224112042
DOI https://dx.doi.org/10.2174/0929867329666220224112042 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Perspectives on Medicinal Properties of Benzoquinone Compounds
Mini-Reviews in Medicinal Chemistry Current Applications of Artificial Neural Networks in Biochemistry with Emphasis on Cancer Research
Current Biochemical Engineering (Discontinued) Recent Advances in the Post-Column Derivatization for the Determination of Mycotoxins in Food Products and Feed Materials by Liquid Chromatography and Fluorescence Detection
Current Analytical Chemistry An Ion Mobility Assisted Data Independent LC-MS Strategy for the Analysis of Complex Biological Samples
Current Analytical Chemistry The Influences of Aconitine, an Active/Toxic Alkaloid from Aconitum, on the Oral Pharmacokinetics of CYP3A Probe Drug Buspirone in Rats
Drug Metabolism Letters Microarrays in Brain Research: Data Quality and Limitations
Current Genomics Electrochemical Approaches Employed for Sensing the Antioxidant Capacity Exhibited by Vegetal Extracts: A Review
Combinatorial Chemistry & High Throughput Screening Proteomic Strategies for the Analysis of Carbonyl Groups on Proteins
Current Protein & Peptide Science Biological Effects of Curcumin and Its Role in Cancer Chemoprevention and Therapy
Anti-Cancer Agents in Medicinal Chemistry Purification and Characterizaion of Buffalo Brain Cystatin
Protein & Peptide Letters <i>Uncaria tomentosa</i> (Willd. ex Schult.): Focus on Nutraceutical Aspects
Current Bioactive Compounds A Fluorescent g-C3N4 Nanosensor for Detection of Dichromate Ions
Current Analytical Chemistry Herbal Compounds with Special Reference to Gastrodin as Potential Therapeutic Agents for Microglia Mediated Neuroinflammation
Current Medicinal Chemistry Quantification of Sulfotransferases 1A1 and 1A3/4 in Tissue Fractions and Cell Lines by Multiple Reaction Monitoring Mass Spectrometry
Drug Metabolism Letters Metabolism of Dietary Flavonoids in Liver Microsomes
Current Drug Metabolism One Dimensional GaN Nanostructures: Growth Kinetics and Applications
Nanoscience & Nanotechnology-Asia Drug Repurposing: An Emerging Tool for Drug Reuse, Recycling and Discovery
Current Drug Research Reviews Anti-Aging Property of G2013 Molecule as a Novel Immunosuppressive Agent on Enzymatic and Non-Enzymatic Oxidative Stress Determinants in Rat Model
Current Drug Discovery Technologies Immune-Neuroendocrine Interactions Involving Thymus and Pineal Gland in Stem Cell Therapy of Age-Related Diseases
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Biosynthesis of Silver Nanoparticles from Synechocystis sp to be Used as a Flocculant Agent with Different Microalgae Strains
Current Nanomaterials