Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, and in vitro and in vivo biological activity evaluations
Liver cancer exhibits a high degree of heterogeneity and involves intricate mechanisms. Recent research has revealed the significant role of histone lysine methylation and acetylation in the epigenetic regulation of liver cancer development. In this study, five inhibitors capable of targeting both histone lysine methyltransferase nuclear receptor-binding SET domain 2 (NSD2) and histone deacetylase 2 (HDAC2) were identified using a structure-based virtual screening approach. Notably, DT-NH-1 displayed a potent inhibition of NSD2 (IC50 = 0.08 +/- 0.03 mu M) and HDAC2 (IC50 = 5.24 +/- 0.87 nM). DT-NH-1 also demonstrated a strong anti-proliferative activity against various liver cancer cell lines, particularly HepG2 cells, and exhibited a high level of biological safety. In an experimental xenograft model involving HepG2 cells, DT-NH-1 showed a significant reduction in tumour growth. Consequently, these findings indicate that DT-NH-1 will be a promising lead compound for the treatment of liver cancer with epigenetic dual-target inhibitors.
第一作者机构：[1]Yangzhou Univ, Affiliated Hosp, Dept Med Lab, Yangzhou 225012, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Yangzhou Univ, Affiliated Hosp, Dept Med Lab, Yangzhou 225012, Peoples R China[3]Guangzhou Univ Chinese Med, Guangdong Prov Hosp Chinese Med, Dept Lab Med, Affiliated Hosp 2, Guangzhou, Peoples R China[4]Guangzhou Univ Chinese Med, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China[*1]Department of Laboratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China[*2]Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
推荐引用方式(GB/T 7714)：
Jin Xing,Wang Yuting,Chen Jing,et al.Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, and in vitro and in vivo biological activity evaluations[J].JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY.2024,39(1):doi:10.1080/14756366.2023.2289355.
APA：
Jin, Xing,Wang, Yuting,Chen, Jing,Niu, Miaomiao,Yang, Yang...&Bao, Guangyu.(2024).Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, and in vitro and in vivo biological activity evaluations.JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY,39,(1)
MLA：
Jin, Xing,et al."Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, and in vitro and in vivo biological activity evaluations".JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 39..1(2024)
