Targeting methionine aminopeptidase 2 in cancer, obesity, and autoimmunity

For over three decades, methionine aminopeptidase 2 (MetAP2) has been a tentative drug target for the treatment of cancer, obesity, and autoimmune diseases. Currently, no MetAP2 inhibitors (MetAP2i) have reached the clinic yet, despite considerable investment by major pharmaceutical companies. Here, we summarize the key series of MetAP2i developed to date and discuss their clinical development, progress, and issues. We coalesce the currently disparate knowledge regarding MetAP2i mechanism of action and discuss discrepancies across varied studies. Finally, we highlight the current knowledge gaps that need to be addressed to enable successful development of MetAP2 inhibitors in clinical settings.

Automated summary

MetAP2 has been a potential drug target for over three decades for the treatment of cancer, obesity, and autoimmune diseases, but no MetAP2 inhibitors have successfully reached clinical trials yet despite significant investment by major pharmaceutical companies. This review summarizes the key series of MetAP2 inhibitors developed so far, discusses their clinical progress and issues, and highlights the need to address gaps in knowledge for successful development of MetAP2 inhibitors in clinical settings.