科研之友
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摘要
Immunosuppressants have shown striking achievements in treating autoimmune diseases in recent years. It is urgent to develop more immunosuppressants to provide more options for patients. PO-296 [2-(6-chlorobenzo[d]oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol] was identified as a novel benzoxazole derivative. We observed that it exhibits an obvious immunosuppressive activity to T lymphocytes. PO-296 significantly inhibited the proliferation of activated human T lymphocyte without cytotoxicity. Moreover, PO-296 did not affect the expression of cluster of differentiation (CD)-25 or CD69 but induced T lymphocyte cycle arrest in the G0/G1 phase. Furthermore, PO-296 inhibited interleukin (IL)-6, IL-17, and interferon gamma expression but had no effect on IL-2, IL-4, or IL-10. Yet, importantly, PO-296 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5), increased the phosphorylation of p70S6K, but did not affect the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mitogen-activated protein kinase pathway. In conclusion, these findings indicate that PO-296 inhibits human activated T-lymphocyte proliferation by affecting the janus kinase 3 (JAK3)/STAT5 pathway. PO-296 possesses a potential lead compound for the design and development of new immunosuppressants for the treatment of autoimmune diseases.
