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
-
Pharmacogenetics, Pharmacogenomics and Epigenetics of Nrf2-regulated Xenobioticmetabolizing Enzymes and Transporters by Dietary Phytochemical and Cancer Chemoprevention
Current Drug Metabolism Peroxisome Proliferator-Activated Receptors: Role of Isoform Gamma in the Antineoplastic Effect of Iodine in Mammary Cancer
Current Cancer Drug Targets Isolation of a New Trypsin Inhibitor from the Faba Bean (Vicia faba cv. Giza 843) with Potential Medicinal Applications
Protein & Peptide Letters In Situ Gene Therapy for Prostate Cancer
Current Gene Therapy Design of New Oxazaphosphorine Anticancer Drugs
Current Pharmaceutical Design Active Metabolites Resulting from Decarboxylation, Reduction and Ester Hydrolysis of Parent Drugs
Current Drug Metabolism Regulation of Expression and Function of IDO in Human Dendritic Cells
Current Medicinal Chemistry Detection of Melatonin Production from the Intestinal Epithelium Using Electrochemical Methods
Current Pharmaceutical Design Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling
Current Vascular Pharmacology The Potential of Ellagic Acid as a Possible Antimalarial Drug Candidate
Current Bioactive Compounds Tumor Growth-Promoting Properties of Macrophage Migration Inhibitory Factor
Current Pharmaceutical Design Anticancer Activity of Organogallium(III) Complexes in Colon Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Aurora B: A New Prognostic Marker and Therapeutic Target in Cancer
Current Medicinal Chemistry Going 3D – Cell Culture Approaches for Stem Cell Research and Therapy
Current Tissue Engineering (Discontinued) Mast Cells in Allergic and Inflammatory Diseases
Current Pharmaceutical Design Postoperative Radiotherapy After Radical Prostatectomy: Adjuvant or Salvage?
Current Cancer Therapy Reviews HPV Pathway Profiling: HPV Related Cervical Dysplasia and Carcinoma Studies
Current Pharmaceutical Design Dendritic Cell Immunotherapy for Melanoma
Reviews on Recent Clinical Trials Prostatic Tumor Stroma: A Key Player in Cancer Progression
Current Cancer Drug Targets Rab GTPases, Membrane Trafficking and Diseases
Current Drug Targets