Glutamate carboxypeptidase II (GCPII) is elevated in active inflamed biopsies of both Crohn’s disease and ulcerative colitis patients and is a promising therapeutic target for the treatment of IBD. We have previously presented the development and characterization of a first-in-class, gut-restricted, and orally active GCPII inhibitor, (S)-IBD3540, and have shown that oral (S)-IBD3540 attenuates disease severity in multiple murine colitis models, including acute dextran sulfate sodium (DSS)-induced colitis.