Computational discovery and repurposing of chloramphenicol succinate as a potent P2Y14 receptor antagonist for inflammatory bowel disease therapy

INTRODUCTION: R antagonists face limitations such as poor bioavailability and structural homogeneity, hindering therapeutic development for inflammatory bowel disease (IBD). Drug repurposing offers a promising strategy to bypass traditional drug discovery challenges by leveraging approved drugs with established safety profiles. OBJECTIVES: R antagonists and validate their therapeutic potential for IBD treatment. METHODS: R antagonism assays and cytotoxicity testing. In vivo efficacy was evaluated in a DSS-induced murine colitis model. RESULTS: = -54.04 kcal/mol) superior to reference compounds. In vivo, DB07565 alleviated colitis symptoms, reduced colon shortening, and restored gut barrier integrity by enhancing tight junction protein expression (Claudin-1, ZO-1, Occludin). CONCLUSION: R antagonist with therapeutic efficacy in IBD. Its established safety, oral stability, and optimized ADME/T properties position it as a clinically translatable candidate, underscoring the value of integrating SBVS and drug repurposing for accelerating anti-inflammatory drug discovery.