Mammalian Target of Rapamycin (mTOR) Signalling Pathway-A Potential Target for Cancer Intervention: A Short Overview.

IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rajesh Basnet, Buddha Bahadur Basnet, Radheshyam Gupta, TilBahadur Basnet, Sandhya Khadka, Md Shan Alam
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引用次数: 0

Abstract

Background: The mammalian role of the rapamycin (mTOR) pathway is the practical nutrient-sensitive regulation of animal growth and plays a central role in physiology, metabolism, and common diseases. The mTOR is activated in response to nutrients, growth factors, and cellular energy. The mTOR pathway activates in various cellular processes and human cancer diseases. Dysfunction of mTOR signal transduction is associated with metabolic disorders, cancer for instance.

Objective: In recent years, significant achievements envisaged in developing targeted drugs for cancer. The global impact of cancer continues to grow. However, the focus of disease-modifying therapies remains elusive. The mTOR is a significant target in cancer to be considered for mTOR inhibitors, even though the costs are high. Despite many mTOR inhibitors, potent, selective inhibitors for mTOR are still limited. Therefore, in this review, the mTOR structure and protein-ligand interactions of utmost importance to provide the basis for molecular modelling and structure-based drug design are discussed.

Conclusion: This review introduces the mTOR, its crystal structure, and the latest research on mTOR.Besides, the role of mTOR in cancer, its function, and its regulation are reviewed. In addition, the mechanistic role of mTOR signalling networks in cancer and interaction with drugs that inhibit the development of mTOR and crystal structures of mTOR and its complexes are explored. Finally, the current status and prospects of mTOR-targeted therapy are addressed.

雷帕霉素(mTOR)信号通路的哺乳动物靶点-癌症干预的潜在靶点:简要概述。
背景:雷帕霉素(mTOR)通路在哺乳动物中的作用是对动物生长的实际营养敏感调节,在生理、代谢和常见疾病中起核心作用。mTOR在营养物质、生长因子和细胞能量的作用下被激活。mTOR通路在各种细胞过程和人类癌症疾病中被激活。mTOR信号转导功能障碍与代谢紊乱有关,例如癌症。目的:近年来,癌症靶向药物的开发有望取得重大成果。癌症对全球的影响持续增长。然而,疾病修饰疗法的焦点仍然难以捉摸。尽管mTOR抑制剂的成本很高,但mTOR是癌症中值得考虑的重要靶点。尽管有许多mTOR抑制剂,但有效的、选择性的mTOR抑制剂仍然有限。因此,本文就mTOR的结构及其与蛋白质配体的相互作用进行综述,为分子建模和基于结构的药物设计提供重要依据。结论:本文综述了mTOR及其晶体结构,以及mTOR的最新研究进展。此外,对mTOR在肿瘤中的作用、功能及其调控进行了综述。此外,还探讨了mTOR信号网络在癌症中的机制作用,以及与抑制mTOR发育的药物的相互作用,以及mTOR及其复合物的晶体结构。最后,对mtor靶向治疗的现状和前景进行了展望。
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来源期刊
Current molecular pharmacology
Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
4.90
自引率
3.70%
发文量
112
期刊介绍: Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.
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