Abstract
Methionine aminopeptidases (MetAPs), which remove methionine residue from newly synthesized polypeptide chains, are a class of metalloproteases ubiquitously distributed in both eukaryotes and prokaryotes. MetAP-2 inhibition can induce G1 cell cycle arrest, cytostasis in tumor cells in vitro and inhibition of tumor growth in vivo. The discovery of fumagillin with potent antiangiogenic and antiproliferative activities promoted the development of fumagillin analogues as a novel class of anticancer agents. Early drug discovery efforts have focused on analogs of fumagillin, which irreversibly inhibit MetAP-2 through covalent modification of an epoxide. Several fumagillin analogs, like CKD-732, TNP-470 and PPI-2458, were found to be potent selective inhibitors of MetAP-2 (proteolytic activity) and endothelial cell proliferation. Further, they have entered in clinical trials for the treatment of different types of tumors. Recently, attention has been paid to reversible human MetAP-2 inhibitors, such as bengamides, 2-hydroxy-3-aminoamides, anthranilic acid sulfonamides and triazole analogs, which have demonstrated their potential to inhibit angiogenesis and tumor growth in vivo as well. This review article mainly discussed the development of MetAP-2 inhibitors in cancer therapy and also summarized their structure-activity relationships.
Keywords: Angiogenesis inhibitor, antiangiogenesis, endothelial cells, methionine, metastasis, migration, MetAP-2, cancer, MetAP-2 inhibitors, fumagillin, structure-activity relationship, vascular endothelial growth factor
Current Medicinal Chemistry
Title: The Development of MetAP-2 Inhibitors in Cancer Treatment
Volume: 19 Issue: 7
Author(s): S.-Q. Yin, J.-J. Wang, C.-M. Zhang and Z.-P. Liu
Affiliation:
Keywords: Angiogenesis inhibitor, antiangiogenesis, endothelial cells, methionine, metastasis, migration, MetAP-2, cancer, MetAP-2 inhibitors, fumagillin, structure-activity relationship, vascular endothelial growth factor
Abstract: Methionine aminopeptidases (MetAPs), which remove methionine residue from newly synthesized polypeptide chains, are a class of metalloproteases ubiquitously distributed in both eukaryotes and prokaryotes. MetAP-2 inhibition can induce G1 cell cycle arrest, cytostasis in tumor cells in vitro and inhibition of tumor growth in vivo. The discovery of fumagillin with potent antiangiogenic and antiproliferative activities promoted the development of fumagillin analogues as a novel class of anticancer agents. Early drug discovery efforts have focused on analogs of fumagillin, which irreversibly inhibit MetAP-2 through covalent modification of an epoxide. Several fumagillin analogs, like CKD-732, TNP-470 and PPI-2458, were found to be potent selective inhibitors of MetAP-2 (proteolytic activity) and endothelial cell proliferation. Further, they have entered in clinical trials for the treatment of different types of tumors. Recently, attention has been paid to reversible human MetAP-2 inhibitors, such as bengamides, 2-hydroxy-3-aminoamides, anthranilic acid sulfonamides and triazole analogs, which have demonstrated their potential to inhibit angiogenesis and tumor growth in vivo as well. This review article mainly discussed the development of MetAP-2 inhibitors in cancer therapy and also summarized their structure-activity relationships.
Export Options
About this article
Cite this article as:
Yin S.-Q., Wang J.-J., Zhang C.-M. and Liu Z.-P., The Development of MetAP-2 Inhibitors in Cancer Treatment, Current Medicinal Chemistry 2012; 19 (7) . https://dx.doi.org/10.2174/092986712799320709
DOI https://dx.doi.org/10.2174/092986712799320709 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Review on Triggered Liposomal Drug Delivery with a Focus on Ultrasound
Current Cancer Drug Targets Recent Progress in Phosphoinositide 3-Kinases: Oncogenic Properties and Prognostic and Therapeutic Implications
Current Protein & Peptide Science An Overview of Acute Flaccid Myelitis
CNS & Neurological Disorders - Drug Targets Selenium Compounds and Apoptotic Modulation: A New Perspective in Cancer Therapy
Mini-Reviews in Medicinal Chemistry Specific Targeting of Akt Kinase Isoforms: Taking the Precise Path for Prevention and Treatment of Cancer
Current Drug Targets Clinical Applications of Positron Emission Tomography (PET) Imaging in Medicine: Oncology, Brain Diseases and Cardiology
Current Radiopharmaceuticals Novel Non-Steroidal Anti-Inflammatory Drugs: What we have Learned from Animal Studies
Current Drug Targets - Inflammation & Allergy Estrogen Catechols Detection as Biomarkers in Schistosomiasis Induced Cancer and Infertility
Letters in Drug Design & Discovery Transcriptional Control of the Oxidative Stress Response and Implications of Using Plant Derived Molecules for Therapeutic Interventions in Cancer
Current Medicinal Chemistry Glutamine, Glucose and other Fuels for Cancer
Current Pharmaceutical Design Molecular Evidence of Cryptotanshinone for Treatment and Prevention of Human Cancer
Anti-Cancer Agents in Medicinal Chemistry Current and Potential Use of Citrus Essential Oils
Current Organic Chemistry Chemotherapy for Prostate Cancer
Current Pharmaceutical Design Exploiting Novel Cell Cycle Targets in the Development of Anticancer Agents
Current Cancer Drug Targets Factors Modulating Fibrates Response: Therapeutic Implications and Alternative Strategies
Endocrine, Metabolic & Immune Disorders - Drug Targets Natural Polymeric Nanoparticles for Brain-Targeting: Implications on Drug and Gene Delivery
Current Pharmaceutical Design The Neurokinins: Peptidomimetic Ligand Design and Therapeutic Applications
Current Medicinal Chemistry Modulation of TRAIL-Induced Apoptosis by HDAC Inhibitors
Current Cancer Drug Targets Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway
Anti-Cancer Agents in Medicinal Chemistry The Novel Functions of cGMP-Specific Phosphodiesterase 5 and its Inhibitors in Carcinoma Cells and Pulmonary/Cardiovascular Vessels
Current Topics in Medicinal Chemistry