論文 - 詳細
| RRC ID | 71630 |
|---|---|
| 著者 | Sato Y, Kashiwakura I, Yamaguchi M, Yoshino H, Tanaka T, Ikeda K, Ye Z, Komatsu H, Matsuzaki T, Hosoda M. |
| タイトル | Discovery of a Novel Small-molecule Interleukin-6 Inhibitor Through Virtual Screening Using Artificial Intelligence. |
| ジャーナル | Med Chem |
| Abstract |
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. |
| 巻・号 | 18(6) |
| ページ | 694-700 |
| 公開日 | 2022-1-1 |
| DOI | 10.2174/1573406418666211116144243 |
| PII | MC-EPUB-118865 |
| PMID | 34784877 |
| MeSH | Antibodies, Monoclonal / metabolism Antineoplastic Agents* / pharmacology Artificial Intelligence Cell Proliferation Interleukin-6* / metabolism Interleukin-6* / pharmacology Phosphorylation Signal Transduction |
| IF | 2.577 |
| リソース情報 | |
| ヒト・動物細胞 | 7-TD-1(RCB1190) |