title: Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects.
abstract: Aminopeptidase N (APN)/CD13 (EC 3.4.11.2) is a transmembrane protease present in a wide variety of human tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). APN/CD13 expression is dysregulated in inflammatory diseases and in cancers (solid and hematologic tumors). APN/CD13 serves as a receptor for coronaviruses. Natural and synthetic inhibitors of APN activity have been characterized. These inhibitors have revealed that APN is able to modulate bioactive peptide responses (pain management, vasopressin release) and to influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis). Therefore, inhibition of APN/CD13 may lead to the development of anti-cancer and anti-inflammatory drugs. This review provides an update on the biological and pharmacological profiles of known natural and synthetic APN inhibitors. Current status on their potential use as therapeutic agents is discussed with regard to toxicity and specificity.
authors.affiliation: Unité INSERM 507, Hôpital Necker, Université René Descartes Paris V, Bâtiment Lavoisier, 161 rue de Sèvres, 75015 Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bauvois
authors.forename: Daniel
authors.initials: D
authors.lastname: Dauzonne
mesh_terms: D000818:Animals; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology; D053978:Pentacyclic Triterpenes; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D014315:Triterpenes / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000094062:Betulinic Acid
chemical_list: D004220:Disulfides; D006877:Hydroxamic Acids; C098403:MR 387A; D009842:Oligopeptides; D053978:Pentacyclic Triterpenes; D011480:Protease Inhibitors; D014315:Triterpenes; C098378:psammaplin A; D014443:Tyrosine; D018826:CD13 Antigens; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex; D003474:Curcumin; C010531:actinonin; D000094062:Betulinic Acid