Similar Publications
Discovery of New Nanomolar Selective IRAP Inhibitors.
J Med Chem
February 2025
Univ. Lille, Inserm, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, F-59000 Lille, France.
Among the M1 family of oxytocinase aminopeptidases, insulin-regulated aminopeptidase IRAP, is an emerging drug target implicated in various biological pathways and particularly in MHC-I antigen presentation through amino-terminal trimming of exogenous cross-presented peptides. A few series of inhibitors inspired either by angiotensin IV, one of IRAP substrates, or by bestatin a pan aminopeptidase inhibitor, have been disclosed. However, the variety and number of chemotypes remains relatively limited.
View Article and Find Full Text PDFInhibition of IRAP Enhances the Expression of Pro-Cognitive Markers Drebrin and MAP2 in Rat Primary Neuronal Cells.
Int J Mol Sci
November 2024
The Beijer Laboratory, Department of Pharmaceutical Biosciences, Neuropharmacology and Addiction Research, Biomedical Centre, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
The insulin-regulated aminopeptidase (IRAP; oxytocinase) is part of the M1 aminopeptidase family and is highly expressed in many tissues, including the neocortex and hippocampus of the brain. IRAP is involved in various physiological functions and has been identified as a receptor for the endogenous hexapeptide Angiotensin IV (Ang IV). The binding of Ang IV inhibits the enzymatic activity of IRAP and has been proven to enhance learning and memory in animal models.
View Article and Find Full Text PDFSex- and time-dependent role of insulin regulated aminopeptidase in lipopolysaccharide-induced inflammation.
Front Immunol
October 2024
Department of Physiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Article Synopsis
- IRAP is an enzyme found in various immune cells, and it helps regulate the body's immune response; its genetic variants are linked to survival rates in septic shock patients.
- In a study modeling systemic inflammation from gram-negative sepsis using LPS, immune responses were compared between IRAP knockout and wildtype mice.
- Results showed that IRAP deficiency led to increased activation and pro-inflammatory response in dendritic cells and macrophages, highlighting the enzyme's role in inflammation, which varies by time and sex.
Insulin-regulated aminopeptidase (IRAP) is an enzyme with important biological functions and the target of drug-discovery efforts. We combined in silico screening with a medicinal chemistry optimization campaign to discover a nanomolar inhibitor of IRAP based on a pyrazolylpyrimidine scaffold. This compound displays an excellent selectivity profile versus homologous aminopeptidases, and kinetic analysis suggests it utilizes an uncompetitive mechanism of action when inhibiting the cleavage of a typical dipeptidic substrate.
View Article and Find Full Text PDFGenome-wide mapping of the binding sites of myocyte enhancer factor 2A in chicken primary myoblasts.
Poult Sci
October 2024
Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, PR China; Joint Nutrition Center for Animal Feeding of Sichuan University-Shengliyuan Group. Electronic address:
Myocyte enhancer factor 2A (MEF2A) is a transcription factor that plays a critical role in cell proliferation, differentiation and apoptosis. In contrast to the wide characterization of its regulation mechanism in mammalian skeletal muscle, its role in chickens is limited. Especially, its wide target genes remain to be identified.
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