Screening and identification of novel WDR5 inhibitors Bithionol and Regorafenib： based on the strategy of drug repurposing
SONG Jie1, MIN Jinrong2, XIONG Li1,2, HUANG Yunyuan2
1.Key Laboratory of Biological Resources and Ecology of Pamirs Plateau in Xinjiang Uygur Autonomous Region， College of Life and Geographic Sciences， Kashi University， Kashi 844000， Xinjiang， China；2.Hubei Key Laboratory of Genetic Regulation and Integrative Biology， College of Life Science， Central China Normal University， Wuhan 430079， China
Abstract：As a high-potential therapeutic target， WDR5 has shown broad application prospects in the treatment of hematoma and solid tumor. To date， the small molecule inhibitors developed for WDR5 have focused on its WIN domain， a unique arginine-binding pocket that recruits a variety of molecular partners closely related to cancer pathological processes， leading to the occurrence and development of disease. The strategy of drug repurposing is a drug development method that applies existing treatment methods to new diseases. Due to its advantages of reducing drug risk， shortening clinical evaluation cycle， low cost and high efficiency， it has become a hot topic in current research. In this paper， drug repurposing was used to screen the marketed drugs on a large scale， aiming to find out the novel WDR5-inhibiting compounds. Two old drugs （Bithionol and Regorafenib） were successfully screened through a combination of differential scanning fluorimetry （DSF） and competitive fluorescence labeling experiments， which targeted the WIN site of WDR5 binding. Further verification by molecular docking technology showed that the two old drugs had a high interaction with WDR5. In summary， this paper verifies the practical feasibility of the drug repurposing， lays a solid theoretical foundation for the subsequent development of new and efficient WDR5 inhibitors， and opens up a novel research path， which is expected to bring breakthrough progress for the treatment of hematoma and solid tumor.
宋杰,闵金荣,熊丽,黄运远. 新型WDR5抑制剂Bithionol与Regorafenib的筛选与鉴定[J]. 华中师范大学学报(自然科学版), 2025, 59(6): 902-908.
SONG Jie,MIN Jinrong,XIONG Li,HUANG Yunyuan. Screening and identification of novel WDR5 inhibitors Bithionol and Regorafenib： based on the strategy of drug repurposing. journal1, 2025, 59(6): 902-908.
2025, Vol. 59 
