Aminopeptidase-N/CD13 (EC inhibitors: chemistry, biological evaluations, and therapeutic prospects

Med Res Rev. 2006 Jan;26(1):88-130. doi: 10.1002/med.20044.


Aminopeptidase N (APN)/CD13 (EC 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CD13 Antigens / antagonists & inhibitors*
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology
  • Disulfides / pharmacology
  • Humans
  • Hydroxamic Acids / pharmacology
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Neovascularization, Physiologic / drug effects
  • Neprilysin / antagonists & inhibitors
  • Oligopeptides / pharmacology
  • Pentacyclic Triterpenes
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Protease Inhibitors / therapeutic use*
  • Triterpenes / pharmacology
  • Tyrosine / analogs & derivatives
  • Tyrosine / pharmacology


  • Disulfides
  • Hydroxamic Acids
  • MR 387A
  • Oligopeptides
  • Pentacyclic Triterpenes
  • Protease Inhibitors
  • Triterpenes
  • psammaplin A
  • Tyrosine
  • betulinic acid
  • CD13 Antigens
  • Neprilysin
  • Leucine
  • ubenimex
  • Curcumin
  • actinonin