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A Gut-Restricted Glutamate Carboxypeptidase II Inhibitor Reduces Monocytic Inflammation and Improves Preclinical Colitis

Peters et al., Science Translational Medicine. 2023.

https://www.science.org/doi/10.1126/scitranslmed.abn7491

Many patients with moderate-to-severe inflammatory bowel disease (IBD) do not have adequate disease control, and glutamate carboxypeptidase II (GCPII) offers a promising target for therapeutic development. Researchers generated a class of GCPII inhibitors. They demonstrated that the inhibitor reduced monocytic inflammation in mice and protected against the loss of barrier integrity in primary human colon epithelial air–liquid interface monolayers. Their findings suggest that local inhibition of GCPII could be applied for the development of IBD therapeutics. Supported by ORIP (K01OD030517, T32OD011089), NIGMS, and NCCIH.