A novel vimentin-stabilizing urea compound MXC-017 ameliorates DSS-induced colitis and radiation enteropathy in mice

Abstract

Ulcerative colitis (UC) and radiation enteropathy involve intestinal epithelial injury, barrier dysfunction, and inflammation, but effective treatments remain limited. This study evaluated MXC-017, a novel vimentin-targeting urea compound, in mouse models of dextran sulfate sodium (DSS)-induced colitis and radiation-induced enteropathy. Acute colitis was induced in C57BL/6 mice using 3.5% DSS for seven days, followed by regular water for seven days. Radiation enteropathy was induced by 13 Gy total abdominal irradiation. Mice received MXC-017 (150 mg/kg) or vehicle. Disease activity, intestinal permeability, inflammatory and epithelial markers, and histopathology were assessed. MXC-017's effects on cancer stem cell frequency, sphere formation, and migration were also examined in PC-3 and DU-145 prostate cancer cells. MXC-017 reduced DSS-induced colitis severity, accelerated weight recovery, lowered disease activity, partially preserved colon length, and restored barrier function. It also reduced proinflammatory cytokines, macrophage infiltration, epithelial injury, and goblet cell loss while preserving epithelial proliferation and markers of intestinal stem cell function and tight-junction integrity. Following irradiation, MXC-017 improved weight recovery, reduced intestinal permeability, preserved epithelial architecture, and partially mitigated villus shortening. Importantly, MXC-017 did not protect prostate cancer stem cells from radiation. Instead, it reduced stem cell frequency, sphere-forming capacity, and cancer cell migration. These findings support vimentin targeting with MXC-017 as a potential treatment for UC and radiation-induced intestinal toxicity and as an adjunct to radiotherapy for pelvic and abdominal malignancies.