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Targeting methionine aminopeptidase 2 in cancer, obesity, and autoimmunity.
- Source :
-
Trends in Pharmacological Sciences . Oct2021, Vol. 42 Issue 10, p870-882. 13p. - Publication Year :
- 2021
-
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. Spanning decades, pharmacological inhibition of methionine aminopeptidase 2 (MetAP2) has been pursued to treat diseases including cancer, obesity, and inflammatory diseases. Irreversible MetAP2 inhibitors have consistently failed in clinical trials due either to lack of efficacy or side effects undermining efficacy, some of which may be due to off-target activity. Limited information regarding mode of action and a lack of consistency between clinical applications and drug development efforts have hindered the progress of MetAP2 inhibitors. Mechanistic insight into MetAP2 inhibitor mode of action, particularly a clear understanding of the MetAP2 substrates driving efficacy, will guide the safe application of MetAP2 inhibitors to treat human disease. [ABSTRACT FROM AUTHOR]
- Subjects :
- *OBESITY
*METHIONINE
*DRUG target
*AUTOIMMUNITY
*AUTOIMMUNE diseases
Subjects
Details
- Language :
- English
- ISSN :
- 01656147
- Volume :
- 42
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Trends in Pharmacological Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 152394951
- Full Text :
- https://doi.org/10.1016/j.tips.2021.07.004