Liu Yuzheng, Luo Dan, Leng Hongwen, Gu Chaolun, Ding Qingrong, Zhao Lin, Chao Xinxin, Wang Hanxia, He Yueteng, Zhu Silu, Ai Guanhua, Peng Weijie
Jiangxi Academy of Medical Sciences, and Hospital of Nanchang University, Bayi Road 461, Nanchang, 330006, Jiangxi, People's Republic of China.
School of Basic Medicine, Medical College, Nanchang University, Bayi Road 461, Nanchang, 330006, Jiangxi, People's Republic of China.
Sci Rep. 2025 Apr 1;15(1):11092. doi: 10.1038/s41598-025-95464-2.
Autotaxin (ATX) is considered as a serum marker of hepatic fibrosis, which is positively correlated with the degree of hepatic fibrosis. However, there are no clinical studies on anti-hepatic fibrosis drugs targeting ATX. This study attempts to find novel ATX small molecule inhibitors based on virtual screening methods including two-dimensional similarity search, pharmacophore screening, molecular docking, drug-like properties and ADMET filtration, combined with biological evaluation. An ATX inhibitor (IC50 = 43.05 µmol/L) is discovered by our screening strategy. In vivo result show that the novel ATX inhibitor represents excellent anti-hepatic fibrosis effects in mice. This screening strategy had potential significance for the discovery of ATX inhibitors in the future.
自分泌运动因子（ATX）被认为是肝纤维化的血清标志物，它与肝纤维化程度呈正相关。然而，目前尚无针对ATX的抗肝纤维化药物的临床研究。本研究试图基于二维相似性搜索、药效团筛选、分子对接、类药性质和ADMET筛选等虚拟筛选方法，并结合生物学评价，寻找新型ATX小分子抑制剂。通过我们的筛选策略发现了一种ATX抑制剂（IC50 = 43.05 µmol/L）。体内实验结果表明，该新型ATX抑制剂在小鼠体内具有优异的抗肝纤维化作用。这种筛选策略对未来发现ATX抑制剂具有潜在意义。
