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
-
Overview of Angiogenesis and the use of Bevacizumab in Patients with Malignant Gliomas
Current Signal Transduction Therapy Taming Oncogenic Signaling at Protein Interfaces: Challenges and Opportunities
Current Topics in Medicinal Chemistry Polymeric Nanomicelles of Soluplus® as a Strategy for Enhancing the Solubility, Bioavailability and Efficacy of Poorly Soluble Active Compounds
Current Nanomedicine Mesenchymal Stem Cells: Key Actors in Tumor Niche
Current Stem Cell Research & Therapy Pharmacological Intervention at CCR1 and CCR5 as an Approach for Cancer: Help or Hindrance
Current Topics in Medicinal Chemistry Cation-Responsive MRI Contrast Agents Based on Gadolinium(III)
Current Inorganic Chemistry (Discontinued) Preparation of Doughnut-like Nanocomposite Colloidal Crystal Particles with Enhanced Light Diffraction Using Drying Self-assembly Method
Current Nanoscience Na<sup>+</sup>/K<sup>+</sup> ATPase Inhibitors in Cancer
Current Drug Targets Exploring a Novel Target Treatment on Breast Cancer: Aloe-emodin Mediated Photodynamic Therapy Induced Cell Apoptosis and Inhibited Cell Metastasis
Anti-Cancer Agents in Medicinal Chemistry Drug Targeting to the Brain - A Review
Current Nanoscience Cytochrome P450-based Gene Therapy for Cancer Treatment: From Concept to the Clinic
Current Drug Metabolism The Therapeutic Potential of miR-7 in Cancers
Mini-Reviews in Medicinal Chemistry Decreasing the Metastatic Potential in Cancers - Targeting the Heparan Sulfate Proteoglycans
Current Drug Targets Endothelin-1 and Angiogenesis in Cancer
Current Vascular Pharmacology Ex Vivo Liver – Directed Gene Therapy for the Treatment of Metabolic Diseases: Advances in Hepatocyte Transplantation and Retroviral Vectors
Current Gene Therapy Intraoperative Magnetic Resonance Imaging
Current Medical Imaging Recent Patents Reveal Microtubules as Persistent Promising Target for Novel Drug Development for Cancers
Recent Patents on Anti-Infective Drug Discovery Protein Kinase C Isozymes as Potential Targets for Anticancer Therapy
Current Cancer Drug Targets miR-629-3p Level Significantly Predicts Prognosis in Glioblastoma Patients Treated with Temozolomide Chemotherapy
Current Signal Transduction Therapy Recent Developments in Chimeric NSAIDs as Anticancer Agents: Teaching an Old Dog a New Trick
Mini-Reviews in Medicinal Chemistry