Abstract
Mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. mTOR signaling is often dysregulated in various human diseases and thus attracts great interest in developing drugs that target mTOR. Currently it is known that mTOR functions as two complexes, mTOR complex 1/2 (mTORC1/2). Rapamycin and its analogs (all termed rapalogs) first form a complex with the intracellular receptor FK506 binding protein 12 (FKBP12) and then bind a domain separated from the catalytic site of mTOR, blocking mTOR function. Rapalogs are selective for mTORC1 and effective as anticancer agents in various preclinical models. In clinical trials, rapalogs have demonstrated efficacy against certain types of cancer. Recently, a new generation of mTOR inhibitors, which compete with ATP in the catalytic site of mTOR and inhibit both mTORC1 and mTORC2 with a high degree of selectivity, have been developed. Besides, some natural products, such as epigallocatechin gallate (EGCG), caffeine, curcumin and resveratrol, have been found to inhibit mTOR as well. Here, we summarize the current findings regarding mTOR signaling pathway and review the updated data about mTOR inhibitors as anticancer agents.
Keywords: mTOR, mTORC1, mTORC2, inhibitor, rapamycin, rapalogs, cancer.
Anti-Cancer Agents in Medicinal Chemistry
Title: Updates of mTOR Inhibitors
Volume: 10 Issue: 7
Author(s): Hongyu Zhou, Yan Luo and Shile Huang
Affiliation:
Keywords: mTOR, mTORC1, mTORC2, inhibitor, rapamycin, rapalogs, cancer.
Abstract: Mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. mTOR signaling is often dysregulated in various human diseases and thus attracts great interest in developing drugs that target mTOR. Currently it is known that mTOR functions as two complexes, mTOR complex 1/2 (mTORC1/2). Rapamycin and its analogs (all termed rapalogs) first form a complex with the intracellular receptor FK506 binding protein 12 (FKBP12) and then bind a domain separated from the catalytic site of mTOR, blocking mTOR function. Rapalogs are selective for mTORC1 and effective as anticancer agents in various preclinical models. In clinical trials, rapalogs have demonstrated efficacy against certain types of cancer. Recently, a new generation of mTOR inhibitors, which compete with ATP in the catalytic site of mTOR and inhibit both mTORC1 and mTORC2 with a high degree of selectivity, have been developed. Besides, some natural products, such as epigallocatechin gallate (EGCG), caffeine, curcumin and resveratrol, have been found to inhibit mTOR as well. Here, we summarize the current findings regarding mTOR signaling pathway and review the updated data about mTOR inhibitors as anticancer agents.
Export Options
About this article
Cite this article as:
Zhou Hongyu, Luo Yan and Huang Shile, Updates of mTOR Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2010; 10 (7) . https://dx.doi.org/10.2174/187152010793498663
DOI https://dx.doi.org/10.2174/187152010793498663 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- 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
Related Articles
-
The Potential Role of Peritumoral Apparent Diffusion Coefficient Evaluation in Differentiating Glioblastoma and Solitary Metastatic Lesions of the Brain
Current Medical Imaging High Expression of miR-483-5p Predicts Chemotherapy Resistance in Epithelial Ovarian Cancer
MicroRNA Genomic Signatures for Individualized Treatment of Malignant Tumors
Current Drug Discovery Technologies Targeted Drug Delivery: Trends and Perspectives
Current Drug Delivery Natural Product-Inspired Synthesis of Thiazolidine and Thiazolidinone Compounds and their Anticancer Activities
Current Pharmaceutical Design Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions
Current Drug Targets Prognostic and Predictive Biomarkers in Colorectal Cancer. From the Preclinical Setting to Clinical Practice
Current Cancer Drug Targets Growth Retardation of Poorly Transfectable Tumor by Multiple Injections of Plasmids Encoding PE40 Based Targeted Toxin Complexed with Polyethylenimine
Current Gene Therapy Alpha-Emitters for Immuno-Therapy: A Review of Recent Developments from Chemistry to Clinics
Current Topics in Medicinal Chemistry Identification of Glioma Specific Genes as Diagnostic and Prognostic Markers for Glioma
Current Bioinformatics Biocompatible Targeting Hydrogels for Breast Cancer Treatment
Mini-Reviews in Medicinal Chemistry Natural Products Targeting Cancer Stem Cells: A Revisit
Current Medicinal Chemistry Current Therapeutic Alternatives and New Perspectives in Glioblastoma Multiforme
Current Medicinal Chemistry Preparation and <I>In Vitro/Vivo</I> Evaluation of Folate-conjugated Pluronic F87-PLGA/TPGS Mixed Nanoparticles for Targeted Drug Delivery
Current Drug Delivery Fiber-Optic Technologies in Laser-Based Therapeutics: Threads for a Cure
Current Pharmaceutical Biotechnology Bioengineered 3D Scaffolds in Cancer Research: Focus on Epithelial to Mesenchymal Transition and Drug Screening
Current Pharmaceutical Design Targeted Enzyme Prodrug Therapies
Mini-Reviews in Medicinal Chemistry Membrane Transporters in Physiological Barriers of Pharmacological Importance
Current Pharmaceutical Design The Insulin-Like Growth Factor (IGF) Signaling Pathway: Strategies for Successful Therapeutic Tasks in Cancer Treatment
Current Cancer Therapy Reviews Therapeutic Targets for the Management of Peripheral Nerve Injury- Induced Neuropathic Pain
CNS & Neurological Disorders - Drug Targets