Aminopeptidase N: a multifunctional and promising target in medicinal chemistry

Aminopeptidase N (APN) is a zinc metalloproteinase present in almost all types of organisms and has various functions. Many of them are unrelated to its catalytic activity, which is why APN is sometimes classified as a moonlighting enzyme. APN is involved in carcinogenesis and angiogenesis. It also works as an entrance receptor for some coronaviruses and acts as a mediator during skin inflammation. Additionally, APN removes and helps to recycle regulatory proteins including neuropeptides, which is why its inhibitors hold therapeutic potential for a wide range of diseases, making the design and development of such molecules highly desirable. Some of them, such as bestatin or tosedostat, have already been tested as therapeutics with partial success. This article aims to bring an overview of multiple APN functions and implications for various diseases and their inhibitors which have already been prepared, and to suggest areas where the development of inhibitors may be promising in the future.