Hu Li, PhD | Chinese Academy of Medical Sciences; Danqing Song, PhD; Zonggen Peng, PhD; Yonghua Liu, PhD; Jingyang Zhu, PhD; Ning Li, MS
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2025
Diabetes, fatty liver disease, and other chronic conditions associated with glucose and lipid metabolism exhibit complex etiologies and frequently coexist with multiple comorbidities. Current drug development faces significant challenges in reversing core pathophysiological processes. In response, we have ingeniously conjugated berberine, a natural agent known for its glucose- and lipid-lowering properties, with bicyclol, a hepatoprotective and anti-inflammatory compound, to formulate a novel oral small molecule. This innovative drug exerts synergistic actions across multiple targets. In an early mouse model of metabolic dysfunction-associated steatotic liver disease (MASH), it exhibited superior efficacy compared to both the physical combination of its components and the marketed drug Resmetirom, particularly in its ability to lower glucose and lipid levels, protect liver function, and improve hepatic pathology, all while maintaining a favorable safety profile. The current project aims to further assess the therapeutic effects of our novel compound in animal models of diabetes, MASH, and related multimorbidity conditions. Additionally, we intend to optimize large-scale synthesis processes, characterize its pharmacokinetic and safety profiles, and elucidate its unique multi-target and sequential synergistic mechanisms, particularly those involving the gut-liver axis and metabolic/inflammatory pathways, thereby facilitating subsequent translation into clinical research.