The in vitro and in vivo study of a pyrazole derivative, J-1063, as a novel anti-liver fibrosis agent : Synthesis, biological evaluation, and mechanistic analysis
Copyright © 2022 Elsevier Inc. All rights reserved..
In the present study, we completed the synthesis of a pyrazole derivative J-1063 and evaluated the kinase inhibitory activity of J-1063 activin receptor-like kinase 5 (ALK5) and p38α mitogen-activated protein (MAP) in the enzymatic assay. We evaluated anti-fibrotic effects of J-1063 on TGF-β-induced hepatic stellate cells activation and TAA induced mice liver fibrosis. J-1063 showed much prior anti-fibrotic effects than those with LY2157299. Our data revealed that J-1063 exerted anti-fibrotic activity by inhibiting TGF-βR1 (ALK5), which is likely related to the inhibition of TGF-β--Smad signaling and NLRP3 inflammasome activation. The results suggest that J-1063 might be potential candidates for further anti-liver fibrosis drug development.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:122 |
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| Enthalten in: |
Bioorganic chemistry - 122(2022) vom: 01. Mai, Seite 105715 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zheng, Guang-Hao [VerfasserIn] |
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| Links: |
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| Themen: |
3QD5KJZ7ZJ |
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| Anmerkungen: |
Date Completed 06.04.2022 Date Revised 08.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bioorg.2022.105715 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM338103163 |
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| 100 | 1 | |a Zheng, Guang-Hao |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The in vitro and in vivo study of a pyrazole derivative, J-1063, as a novel anti-liver fibrosis agent |b Synthesis, biological evaluation, and mechanistic analysis |
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| 500 | |a Date Revised 08.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Inc. All rights reserved. | ||
| 520 | |a In the present study, we completed the synthesis of a pyrazole derivative J-1063 and evaluated the kinase inhibitory activity of J-1063 activin receptor-like kinase 5 (ALK5) and p38α mitogen-activated protein (MAP) in the enzymatic assay. We evaluated anti-fibrotic effects of J-1063 on TGF-β-induced hepatic stellate cells activation and TAA induced mice liver fibrosis. J-1063 showed much prior anti-fibrotic effects than those with LY2157299. Our data revealed that J-1063 exerted anti-fibrotic activity by inhibiting TGF-βR1 (ALK5), which is likely related to the inhibition of TGF-β--Smad signaling and NLRP3 inflammasome activation. The results suggest that J-1063 might be potential candidates for further anti-liver fibrosis drug development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Liver fibrosis | |
| 650 | 4 | |a Pyrazole derivative | |
| 650 | 4 | |a Smad | |
| 650 | 4 | |a TGF-β | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Smad Proteins |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 650 | 7 | |a pyrazole |2 NLM | |
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| 700 | 1 | |a Liu, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Fang Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhi-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yin-Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Yong-Ce |e verfasserin |4 aut | |
| 700 | 1 | |a Lan, Xiao-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yan-Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Nan, Ji-Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Cheng Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Lian, Li-Hua |e verfasserin |4 aut | |
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