Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis

Song, Nazi; Xu, Hao; Liu, Jiahua; Zhao, Qian; Chen, Hui; Ye, Zhibin; Yang, Runling; Luo, Zhiteng; Liu, Qi; Ouyang, Jianmei; Wu, Shuohan; Luo, Suijia; Ye, Shuyin; Lin, Runfeng; Sun, Xi; Xie, Junqiu; Lan, Tian; Wu, Zhongdao; Wang, Rui; Jiang, Xianxing

doi:10.1016/j.apsb.2021.12.016

Cited by 15 publications

(16 citation statements)

References 49 publications

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“…Cyclic peptides have been shown to have increased selectivity, potency, bioavailability, and metabolic stability compared to linear peptides . Inspired by our recent efforts for studies on the design of functional peptide skeletons, structure–activity relationship, and pharmacological mechanism in the field of liver fibrosis treatment, ,,, we herein introduced the design and discovery of types of novel cyclic peptides as an inhibitor of EDPs–EBP interaction for the treatment of liver fibrosis. In this study, the structure–activity relationship of the V14 structure-oriented peptides was first studied to identify the specific amino acid residues within the peptide sequence that are essential for its antifibrosis activity.…”

Section: Introductionmentioning

confidence: 99%

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Design and Discovery of Novel Cyclic Peptides as EDPs–EBP Interaction Inhibitors for the Treatment of Liver Fibrosis

Song

Tang

et al. 2023

J. Med. Chem.

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Liver fibrosis is the undesirable result of excessive deposition of the extracellular matrix (ECM), and elastin is known as one of the key ECM components. Under specific pathological conditions, elastin undergoes degradation to produce elastin-derived peptides (EDPs), which bind to elastin-binding protein (EBP) to activate corresponding signal pathways, thus accelerating fibrosis progression. Herein, we describe the discovery of novel cyclic peptides that function as potent and stable inhibitors to interfere with the peptide–protein interaction between EDPs and EBP. Remarkably, C XJ -2 exhibited potent activities to inhibit the PI3K/ERK pathway and decrease hepatic stellate cell proliferation and migration. The subsequent in vivo study demonstrated that C XJ -2 possessed potent antifibrotic efficacy in ameliorating CCl4-induced liver fibrosis. This work provides a successful pharmacological strategy for the development of novel inhibitors of EDPs–EBP interaction, which sheds new light on how cyclic peptides disrupt peptide–protein interaction and may also provide new structure-oriented therapeutic candidates in liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

“…The pathophysiological effects have been found to be related to the activation of ERC . The binding of EDPs to EBP can activate Neu-1, cause the sustained activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, and accelerate cell proliferation and elastin expression in fibroblasts. − …”

Section: Introductionmentioning

confidence: 99%

Design and Discovery of Novel Cyclic Peptides as EDPs–EBP Interaction Inhibitors for the Treatment of Liver Fibrosis

Song

Tang

et al. 2023

J. Med. Chem.

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“…11,12 As a result, researchers have been stimulated to find antifibrotic treatments because liver fibrosis was proven to be reversible. [13][14][15][16] The field of liver fibrosis is flourishing due to continued experimental advances and exciting advances in the treatment of chronic liver disease. 4,6,[15][16][17] Over the years, many research articles have been published, as well as a number of review articles on different aspects of liver fibrosis, such as diagnosis, mechanisms, and treatment.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15][16] The field of liver fibrosis is flourishing due to continued experimental advances and exciting advances in the treatment of chronic liver disease. 4,6,[15][16][17] Over the years, many research articles have been published, as well as a number of review articles on different aspects of liver fibrosis, such as diagnosis, mechanisms, and treatment. 3,13,[17][18][19][20] Whereas these studies have provided initial insights into the field of liver fibrosis, most have only focused on specific issues in the field of liver fibrosis.…”

Section: Introductionmentioning

confidence: 99%

“…Research has proven that liver fibrosis is a reversible wound healing process, a critical pre‐cirrhotic stage of liver cirrhosis that, if left untreated, can eventually develop into hepatocellular carcinoma 11,12 . As a result, researchers have been stimulated to find antifibrotic treatments because liver fibrosis was proven to be reversible 13–16 . The field of liver fibrosis is flourishing due to continued experimental advances and exciting advances in the treatment of chronic liver disease 4,6,15–17 .…”

Section: Introductionmentioning

confidence: 99%

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A bibliometric and visualized analysis of liver fibrosis from 2002 to 2022

Zhao

Liang

Zhai

et al. 2022

J of Gastro and Hepatol

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Fibrosis of the liver is a degenerative alteration that occurs in the majority of chronic liver disorders. Further progression can lead to cirrhosis, liver failure, and hepatocellular carcinoma, which can seriously affect the health and lives of patients. The field of liver fibrosis research has flourished in the last 20 years, with approximately 9000 articles retrieved from the Web of Science Core Collection database alone. In order to identify future research hotspots and potential paths in a thorough and scientifically reliable manner, it is important to organize and visualize the research on this topic from a holistic and very general perspective. This study used bibliometric analysis with CiteSpace and VOSviewer software to provide a quantitative analysis, hotspot mining, and commentary of articles published in the field of liver fibrosis over the last 20 years. This bibliometric analysis contains a total of 8994 articles with 45667 authors from 6872 institutions in 97 countries, published in 1371 journals and citing 156 309 references. The literature volume has steadily increased over the last 20 years. Research has focused on gastroenterology and hepatology, pharmacology and pharmacy, and medicine, research, and experimental areas. We found that the pathological mechanisms, diagnostic and quantitative methods, etiology, and antifibrotic strategies constitute the knowledge structure of liver fibrosis. Finding mechanisms for liver fibrosis regression, identifying precise noninvasive diagnostic and prognostic biomarkers, and creating efficient liver fibrosis patient treatments are the main goals of current research.

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Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis

Zhao,

Dong,

Liu

et al. 2024

Acta Pharmaceutica Sinica B

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Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis

Cited by 15 publications

References 49 publications

Design and Discovery of Novel Cyclic Peptides as EDPs–EBP Interaction Inhibitors for the Treatment of Liver Fibrosis

Design and Discovery of Novel Cyclic Peptides as EDPs–EBP Interaction Inhibitors for the Treatment of Liver Fibrosis

A bibliometric and visualized analysis of liver fibrosis from 2002 to 2022

Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis

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