P135 ORALLY ADMINISTERED FOLH1/GCPII INHIBITORS AS NOVEL THERAPEUTICS IN INFLAMMATORY BOWEL DISEASE (IBD)

The folate hydrolase gene (FOLH1), which encodes for the enzyme glutamate carboxypeptidase II (GCPII), has been implicated in the pathogenesis of inflammatory bowel disease (IBD) where it exhibits a robust 300-1000% increase in enzymatic activity in intestinal biopsies collected from Crohn’s Disease and Ulcerative Colitis patients. We have previously shown that systemic administration of the GCPII inhibitor 2-PMPA (IC50=300 pM) led to significant improvement in disease activity index in three commonly used murine models of IBD: DSS-colitis, TNBS-colitis and spontaneous colitis of IL10-/- mice.

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