CTGF公司
纤维化
肝纤维化
化学
癌症研究
结缔组织
药理学
病理
生物
受体
生长因子
生物化学
医学
作者
Yunyang Bao,Tianyu Niu,Jingyang Zhu,Yuheng Mei,Yulong Shi,R. Meng,Qiong-Lu Duan,Na Zhang,Tianyun Fan,Yanxiang Wang,Yudong Pang,Yinghong Li,Hongwei He,Danqing Song
标识
DOI:10.1021/acs.jmedchem.3c00286
摘要
A series of new tricyclic matrinane derivatives were continuously synthesized and evaluated for their inhibitory effects on genes and proteins related to hepatic fibrosis at the cellular level, including collagen type I α1 chain (COL1A1), α smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and matrix metalloprotein 2 (MMP-2). Among them, compound 6k exerted an appealing potency and significantly reduced liver injury and fibrosis in both bile duct ligation (BDL) rats and Mdr2 knockout mice. An activity-based protein profiling (ABPP) assay indicated that 6k might directly bind to Ewing sarcoma breakpoint region 1 (EWSR1) to inhibit its function and affect the expression of downstream liver fibrosis-related genes and thus regulate liver fibrosis. These results provided a potential novel target for the treatment of liver fibrosis and powerful information for the development of tricyclic matrinanes into promising anti-hepatic fibrosis agents.
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