Development and Biological Evaluation of a GLUT-Inhibiting Theranostic Agent, MF48, for Colorectal Cancer Therapy

Aberrant glucose utilization is a hallmark of malignant cells and represents an attractive target for anticancer intervention. Here, we describe development of Medical Fluorophore 48 (MF48), a synthesized compound that simultaneously inhibits glucose metabolism and enables optical imaging, thereby exerting potent in vivo anticancer activity against colorectal cancer. MF48 significantly downregulated the expression of glucose transporters GLUT1-4 in colorectal cancer (CRC) cells, resulting in suppressed glucose uptake. Consequently, MF48 elicited selective cytotoxicity in CRC cells through activation of the p53/p21/caspase-3 apoptotic signaling. In vivo fluorescent imaging, based on the strong red-emissive fluorescence of MF48, visualized its distribution in living mice, while ex vivo imaging confirmed its accumulation within tumors. Importantly, repeated administration of MF48 significantly inhibited tumor growth in a CRC mouse model by decreasing Glut expression in tumor tissues without inducing systemic toxicity. Taken together, these findings establish MF48 as a promising glucose-targeting theranostic agent for CRC therapy, while highlighting its scaffold as a synthetically accessible, modular fluorophore platform that enables biological modulation while preserving intrinsic photophysical properties through late-stage functionalization.