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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.
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http://dx.doi.org/10.2174/1874467217666230331081959 | DOI Listing |
J Innate Immun
August 2025
Piezo-type mechanosensitive ion channel component 1 (Piezo1) is an evolutionarily conserved and multifunctional mechanosensitive ion channel protein that has emerged as a significant contributor to the pathogenesis of inflammatory bowel disease (IBD). Piezo1 plays a crucial role in regulating intestinal barrier integrity, immune responses, and the intestinal nervous system, thereby influencing disease progression. Its expression patterns correlate with disease severity and inflammatory markers in IBD patients, indicating its potential as a diagnostic and prognostic biomarker.
View Article and Find Full Text PDFExp Neurol
September 2025
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Anshan Road, Heping District, Tianjin 300052, China. Electronic address:
Alcohol Clin Exp Res (Hoboken)
September 2025
Department of Neuroscience and Experimental Therapeutics, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Background: Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorder (FASD) and is associated with various cognitive and sensory impairments, including olfactory dysfunction. While both genetic and environmental factors contribute to olfactory dysfunction, PAE is considered a significant factor affecting brain development, including the olfactory system. In this study, we investigated the impact of PAE on the developing olfactory bulb (OB), specifically focusing on OB RGCs-radial glial cells that give rise to OB projection neurons.
View Article and Find Full Text PDFChem Biol Interact
September 2025
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China; Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China; Hubei Shizhen Laboratory, Wuhan,430061, People 's
Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with insidious onset, limited treatments, and poor prognosis. Recent studies show celecoxib exerts marked cytotoxic effects on cholangiocarcinoma cell lines, suggesting its potential as an iCCA therapy. However, the potential molecular and cellular mechanisms that link celecoxib treatment to its toxicological outcomes remain unclear.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Xianyang, China. Electronic address:
Pancreatic adenocarcinoma (PAAD) lacks effective therapies due to complex macromolecular signaling networks. Here, we identified the natural compound Trienomycin A (TA) as a potent binder and degrader of the key signaling adaptor protein Insulin Receptor Substrate 1 (IRS1), disrupting its macromolecular assembly in insulin-like growth pathways. Through integrated biochemical, cellular, and in vivo analyses, we demonstrated that TA directly bound the phosphotyrosine-binding (PTB) domain of IRS1, inducing proteasomal degradation of this critical macromolecular hub mediated by the E3 ubiquitin ligase FBXW8.
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