2. Academic Validation
  3. Discovery and preclinical evaluations of GST-HG131, a novel HBV antigen inhibitor for the treatment of chronic hepatitis B infection

Discovery and preclinical evaluations of GST-HG131, a novel HBV antigen inhibitor for the treatment of chronic hepatitis B infection

  • Bioorg Med Chem Lett. 2022 Nov 1;75:128977. doi: 10.1016/j.bmcl.2022.128977.
Yanbin Hu 1,  Fei Sun 1,  Qiang Yuan 1,  Jinhua Du 1,  Lihong Hu 1,  Zhengxian Gu 2,  Qiong Zhou 2,  Xiaoting Du 2,  Shibo He 2,  Ya Sun 2,  Qian Wang 2,  Lirong Fan 2,  Lina Wang 2,  Shaohua Qin 2,  Shuhui Chen 2,  Jian Li 2,  Wenqiang Wu 3,  John Mao 3,  Yixin Zhou 3,  Qiaoyun Zhou 3,  George Zhang 3,  Charles Z Ding 4
Affiliations

Affiliations

  • 1 WuXi AppTec, 666 Gaoxin Road, East Lake High-tech Development Zone, Wuhan 430075, China.
  • 2 WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
  • 3 Fujian Akeylink Biotechnology Co.,Ltd, Fujian, China.
  • 4 WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China. Electronic address: [email protected].
PMID: 36089112 DOI: 10.1016/j.bmcl.2022.128977
Abstract

Chronic hepatitis B (CHB) remains a significant health challenge worldwide. The current treatments for CHB achieve less than 10% cure rates, majority of the patients are on therapy for life. Therefore, cure of CHB is a high unmet medical need. HBV surface antigen (HBsAg) loss and seroconversion are considered as the key for the cure. RG7834 is a novel, orally bioavailable small molecule reported to reduce HBV antigens. Based on RG7834 chemistry, we designed and discovered a series of dihydrobenzopyridooxazepine (DBP) series of HBV antigen inhibitors. Extensive SAR studies led us to GST-HG131 with excellent reduction of HBV antigens (both HBsAg and HBeAg) in vitro and in vivo. GST-HG131 improved safety in rat toxicology studies over RG7834. The promising inhibitory activity, together with animal safety enhancement, merited GST-HG131 progressed into clinical development in 2020 (NCT04499443).

Keywords

Chronic hepatitis B (CHB); GST-HG131; HBV cure; HBV surface antigen inhibitor; HBsAg.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-134790
    99.94%, HBV Inhibitor
    HBV