Development of a novel Fc fusion protein dual glucagon‐like peptide‐1 and gastric inhibitory polypeptide receptor agonists

Author:

Jiang Peng1,Sun Ningyuan2,Yang Wen2,Xiao Lin1,Zhou Linjun1,Gu Baohua2,Li Yong2,Li Lijia1,Li Jing2,Li Xiaoping1,Li Wenjia1,Guo Linfeng1ORCID

Affiliation:

1. Dongguan HEC Biopharmaceutical R&D Co., Ltd. Dongguan China

2. Sunshine Lake Pharma Co., Ltd. Dongguan China

Abstract

AbstractAimTo develop and investigate an imbalanced dual gastric inhibitory polypeptide receptor (GIPR)/glucagon‐like peptide‐1 receptor (GLP‐1 R) agonist with Fc fusion protein structure.MethodsWe designed and constructed an Fc fusion protein that is a dual agonist (HEC‐CG115) with an empirically optimized potency ratio for GLP‐1R and GIPR. The long‐term effects of HEC‐CG115 on body weight and glycaemic control were evaluated in diet‐induced obese mice and diabetic db/db mice. Repeat dose toxicity assays were performed to investigate the safety profile of HEC‐CG115 in Sprague‐Dawley rats.ResultsHEC‐CG115 displayed high potency for GIPR and relatively low potency for GLP‐1R, and we labelled it ‘imbalanced’. In animal models, HEC‐CG115 (3 nmol/kg) led to more weight loss than semaglutide at a higher dose (10 nmol/kg) in diet‐induced obese model mice. HEC‐CG115 (one dose every 3 days) reduced fasting blood glucose and glycated haemoglobin levels similar to those after semaglutide (once daily) at the same dose. In a 4‐week subcutaneous toxicity study conducted to assess the biosafety of HEC‐CG115, the no observed adverse effect level was determined to be 3 mg/kg.ConclusionHEC‐CG115 is a novel Fc fusion protein with imbalanced dual agonism that shows superior weight loss, glycaemic control and metabolic improvement in animal models, and has an optimal safety profile according to a repeat‐dose toxicity study. Therefore, the use of HEC‐CG115 appears to be safe and effective for the treatment of obesity and type 2 diabetes.

Publisher

Wiley

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism,Internal Medicine

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3