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
-
Human Sirtuins: An Overview of an Emerging Drug Target in Age-Related Diseases and Cancer
Current Drug Targets Antisense Oligonucleotide Drug Design
Current Pharmaceutical Design Epigenetic Metalloenzymes
Current Medicinal Chemistry Diselenides and Selenocyanates as Versatile Precursors for the Synthesis of Pharmaceutically Relevant Compounds
Current Organic Synthesis The Role of Mass Spectrometry in the “Omics” Era
Current Organic Chemistry Current Biomarkers for Lung Cancer
Current Signal Transduction Therapy Epigenetic Modifications in Acute Lymphoblastic Leukemia: From Cellular Mechanisms to Therapeutics
Current Gene Therapy Glycogen Synthase Kinase 3 as an Anticancer Drug Target: Novel Experimental Findings and Trends in the Design of Inhibitors
Current Pharmaceutical Design Sera/Organ Lysates of Selected Animals Living in Polluted Environments Exhibit Cytotoxicity against Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry 2-Deoxy-D-Ribose, a Downstream Mediator of Thymidine Phosphorylase, Regulates Tumor Angiogenesis and Progression
Anti-Cancer Agents in Medicinal Chemistry The Impact of Combination Therapy with a-Blockers and 5ARIs on the Progression of BPH
Current Drug Targets Pharmacophore Modeling and 3D QSAR Studies of Novel Human Carbonic Anhydrase IX Inhibitors
Letters in Drug Design & Discovery Apoptosis is a Critical Cellular Event in Cancer Chemoprevention and Chemotherapy by Selenium Compounds
Current Cancer Drug Targets Application of 3D Biomimetic Models in Drug Delivery and Regenerative Medicine
Current Pharmaceutical Design Bioactivities of Iridoids
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Current Targets for Anticancer Drug Discovery
Current Drug Targets Targeting Proteasomal Pathways by Dietary Curcumin for Cancer Prevention and Treatment
Current Medicinal Chemistry A Review of Himalayan Medicinal Plants against Cancer
Current Traditional Medicine New Targets, New Agents, and the Evolving Phenomena of Drug Resistance in Cancer
Current Cancer Therapy Reviews Insulin-like Effects of Mt. Fuji Subsoil Water which Conta ins Vanadium on Cultured Cells: Insight from Japan
Current Traditional Medicine