A prodrug of the capsid assembly modulator improved druggability and lowing HBsAg and HBeAg for the treatment of chronic hepatitis B

被引：4

作者：

Chen, Wuhong ^{[1
]}

Gong, Ying ^{[2
,3
]}

Long, Guozhang ^{[1
,3
]}

Wang, Xinran ^{[2
,4
]}

Yang, Yurong ^{[1
,4
]}

Liu, Jia ^{[1
,5
]}

Li, Heng ^{[2
,3
]}

Tong, Xiankun ^{[2
]}

Zhao, Qiliang ^{[1
,3
]}

Yang, Li ^{[2
]}

Zuo, Jianping ^{[2
,3
,4
]}

Hu, Youhong ^{[1
,3
,5
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu ChongZhi Rd, Shanghai 201203, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, 555 Zu ChongZhi Rd, Shanghai 201203, Peoples R China

[3] Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China

[4] Nanjing Univ Chinese Med, Coll Pharm, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Peoples R China

[5] Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, 1st Xiangshan Branch Alley, Hangzhou 310024, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 257卷

基金：

中国国家自然科学基金;

关键词：

HBV; Capsid assembly modulators; Prodrug; Hepatitis B surface antigen; VIRUS INFECTION; RO7049389; DRUG;

D O I：

10.1016/j.ejmech.2023.115485

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

CAMs were disclosed to alter cccDNA levels with sustained hepatitis B surface antigen (HBsAg) loss or sero-conversion in preclinical investigation. Here, we report the discovery of a prodrug Yhhu6669 as CAMs based on the intestinal peptide transporter. This compound exhibited the promising anti-HBV activity with sustained suppression of HBV DNA, as well as HBsAg and HBeAg in the AAV HBV mouse model by oral treatment for 7 weeks and maintained for a further 8 weeks following drug withdraw. Our results show an alternative possibility for a functional cure by specific CAMs and provide the basis for the further mechanism study.

引用

页数：8

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