化学
衍生工具(金融)
成纤维细胞生长因子受体1
癌症研究
立体化学
组合化学
药理学
生物化学
受体
成纤维细胞生长因子
医学
生物
金融经济学
经济
作者
Zhihao Chen,Alessandra Marie Encarnacion,R Rajan,Hailan Yao,Sunwoo Lee,Eunae Kim,Tae‐Hoon Lee
标识
DOI:10.1016/j.ejmech.2024.116335
摘要
Several flavonoids have been shown to exert anti-osteoporosis activity. However, the structure-activity relationship and the mechanism of anti-osteoporosis activity of flavonoids remain unknown. In this study, we prepared a series of novel homoisoflavonoid (HIF) derivatives to evaluate their inhibitory effects on osteoclastogenesis using TRAP-activity in vitro assay. Then, the preliminary structure-activity relationship was studied. Among the evaluated novel flavonoids, derivative 5g exerted the most inhibitory bioactivity on primary osteoclast differentiation without interfering with osteogenesis. It was hence selected for further in vitro, in vivo and mechanism of action investigation. Results show that 5g likely directly binds to the fibroblast growth factor receptor 1 (FGFR1), decreasing the activation of ERK1/2 and IκBα/NF-κB signaling pathways, which in turn blocks osteoclastogenesis in vitro and osteoclastic bone loss in vivo. Our study shows that homoisoflavonoid (HIF) derivatives 5g can serve as a potential novel candidate for treating osteoporosis via inhibition of FGFR1.
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