Discovery of a Novel Small-molecule Interleukin-6 Inhibitor Through Virtual Screening Using Artificial Intelligence
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine involved in various cell functions and diseases. Thus far, several IL-6 inhibitors, such as humanized monoclonal antibody have been used to block excessive IL-6 signaling causing autoimmune and inflammatory diseases. However, anti-IL-6 and anti-IL-6 receptor monoclonal antibodies have some clinical disadvantages, such as a high cost, unfavorable injection route, and tendency to mask infectious diseases. While a small-molecule IL-6 inhibitor would help mitigate these issues, none are currently available.
OBJECTIVE: The present study evaluated the biological activities of identified compounds on IL-6 stimulus.
METHODS: We virtually screened potential IL-6 binders from a compound library using INTerprotein's Engine for New Drug Design (INTENDD®) followed by the identification of more potent IL-6 binders with artificial intelligence (AI)-guided INTENDD®. The biological activities of the identified compounds were assessed with the IL-6-dependent cell line 7TD1.
RESULTS: The compounds showed the suppression of IL-6-dependent cell growth in a dose-dependent manner. Furthermore, the identified compound inhibited expression of IL-6-induced phosphorylation of signal transducer and activator of transcription 3 in a dose-dependent manner.
CONCLUSION: Our screening compound demonstrated an inhibitory effect on IL-6 stimulus. These findings may serve as a basis for the further development of small-molecule IL-6 inhibitors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Medicinal chemistry (Shariqah (United Arab Emirates)) - 18(2022), 6 vom: 16., Seite 694-700 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sato, Yoshiaki [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.04.2022 Date Revised 17.10.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1573406418666211116144243 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM333225686 |
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| 100 | 1 | |a Sato, Yoshiaki |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Discovery of a Novel Small-molecule Interleukin-6 Inhibitor Through Virtual Screening Using Artificial Intelligence |
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| 500 | |a Date Revised 17.10.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine involved in various cell functions and diseases. Thus far, several IL-6 inhibitors, such as humanized monoclonal antibody have been used to block excessive IL-6 signaling causing autoimmune and inflammatory diseases. However, anti-IL-6 and anti-IL-6 receptor monoclonal antibodies have some clinical disadvantages, such as a high cost, unfavorable injection route, and tendency to mask infectious diseases. While a small-molecule IL-6 inhibitor would help mitigate these issues, none are currently available | ||
| 520 | |a OBJECTIVE: The present study evaluated the biological activities of identified compounds on IL-6 stimulus | ||
| 520 | |a METHODS: We virtually screened potential IL-6 binders from a compound library using INTerprotein's Engine for New Drug Design (INTENDD®) followed by the identification of more potent IL-6 binders with artificial intelligence (AI)-guided INTENDD®. The biological activities of the identified compounds were assessed with the IL-6-dependent cell line 7TD1 | ||
| 520 | |a RESULTS: The compounds showed the suppression of IL-6-dependent cell growth in a dose-dependent manner. Furthermore, the identified compound inhibited expression of IL-6-induced phosphorylation of signal transducer and activator of transcription 3 in a dose-dependent manner | ||
| 520 | |a CONCLUSION: Our screening compound demonstrated an inhibitory effect on IL-6 stimulus. These findings may serve as a basis for the further development of small-molecule IL-6 inhibitors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Artificial intelligence | |
| 650 | 4 | |a interleukin-6 | |
| 650 | 4 | |a protein-protein interactions | |
| 650 | 4 | |a signal transducer and activator of transcription 3 | |
| 650 | 4 | |a small molecule inhibitor | |
| 650 | 4 | |a virtual screening | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 700 | 1 | |a Kashiwakura, Ikuo |e verfasserin |4 aut | |
| 700 | 1 | |a Yamaguchi, Masaru |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshino, Hironori |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Takeshi |e verfasserin |4 aut | |
| 700 | 1 | |a Ikeda, Ken |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Zhengmao |e verfasserin |4 aut | |
| 700 | 1 | |a Komatsu, Hirotsugu |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuzaki, Takao |e verfasserin |4 aut | |
| 700 | 1 | |a Hosoda, Masato |e verfasserin |4 aut | |
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