Design, synthesis and biological evaluation of 4-aminoquinoline derivatives as receptor-interacting protein kinase 2 (RIPK2) inhibitors
Receptor-interacting protein kinase 2 (RIPK2) is an essential protein kinase mediating signal transduction by NOD1 and NOD2, which play an important role in regulating immune signalling. In this study, we designed and synthesised a novel series of 4-aminoquinoline-based derivatives as RIPK2 inhibitors. In vitro, compound 14 exhibited high affinity (IC50 = 5.1 ± 1.6 nM) and excellent selectivity to RIPK2 showing in a dendrogram view of the human kinome phylogenetic tree. Bearing favourable lipophilicity and eligible lipophilic ligand efficiency (LipE), compound 14 was selected to investigate cellular anti-inflammatory effect and was identified as a potent inhibitor to reduce the secretion of MDP-induced TNF-α with a dose-dependent manner. Moreover, compound 14 showed moderate stability in human liver microsome. Given these promising results, compound 14 could serve as a favourable inhibitor of RIPK2 for further physiological and biochemical research so as to be used in therapeutic treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Journal of enzyme inhibition and medicinal chemistry - 38(2023), 1 vom: 16. Dez., Seite 282-293 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fan, Tiantian [VerfasserIn] |
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| Links: |
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| Themen: |
4-aminoquinoline |
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| Anmerkungen: |
Date Completed 22.11.2022 Date Revised 25.11.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/14756366.2022.2148317 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM34922031X |
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| 245 | 1 | 0 | |a Design, synthesis and biological evaluation of 4-aminoquinoline derivatives as receptor-interacting protein kinase 2 (RIPK2) inhibitors |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 22.11.2022 | ||
| 500 | |a Date Revised 25.11.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Receptor-interacting protein kinase 2 (RIPK2) is an essential protein kinase mediating signal transduction by NOD1 and NOD2, which play an important role in regulating immune signalling. In this study, we designed and synthesised a novel series of 4-aminoquinoline-based derivatives as RIPK2 inhibitors. In vitro, compound 14 exhibited high affinity (IC50 = 5.1 ± 1.6 nM) and excellent selectivity to RIPK2 showing in a dendrogram view of the human kinome phylogenetic tree. Bearing favourable lipophilicity and eligible lipophilic ligand efficiency (LipE), compound 14 was selected to investigate cellular anti-inflammatory effect and was identified as a potent inhibitor to reduce the secretion of MDP-induced TNF-α with a dose-dependent manner. Moreover, compound 14 showed moderate stability in human liver microsome. Given these promising results, compound 14 could serve as a favourable inhibitor of RIPK2 for further physiological and biochemical research so as to be used in therapeutic treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a NOD | |
| 650 | 4 | |a RIPK2 inhibitor | |
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| 650 | 4 | |a inflammation | |
| 650 | 7 | |a 4-aminoquinoline |2 NLM | |
| 650 | 7 | |a GTE5P5L97N |2 NLM | |
| 650 | 7 | |a Aminoquinolines |2 NLM | |
| 650 | 7 | |a RIPK2 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Receptor-Interacting Protein Serine-Threonine Kinase 2 |2 NLM | |
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| 700 | 1 | |a Ji, Yinchun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Danqi |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Ai, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Bing |e verfasserin |4 aut | |
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