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Targeting methionine aminopeptidase 2 in cancer, obesity, and autoimmunity
Andrea Goya Grocin1, Wouter W Kallemeijn1, Edward W Tate1
1Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, London W12 0BZ, UK; The Francis Crick Institute, London NW1 1AT, UK.
Abstract:
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.
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