The Development of MetAP-2 Inhibitors in Cancer Treatment
| Autor: | Zhao-Peng Liu, Shu-Qiang Yin, Jianxin Wang, Chengcheng Zhang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Angiogenesis
Biology Aminopeptidases Biochemistry Structure-Activity Relationship chemistry.chemical_compound Cyclohexanes In vivo Neoplasms Drug Discovery medicine Humans Structure–activity relationship Fumagillin Enzyme Inhibitors Pharmacology Methionine Drug discovery Organic Chemistry Metalloendopeptidases Cytostasis In vitro Enzyme Activation chemistry Drug Design Fatty Acids Unsaturated Molecular Medicine Sesquiterpenes medicine.drug |
| Zdroj: | Current Medicinal Chemistry. 19:1021-1035 |
| ISSN: | 0929-8673 |
| DOI: | 10.2174/092986712799320709 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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