A benzoxazole derivative PO‐296 inhibits T lymphocyte proliferation by the JAK3/STAT5 signal pathway

Abstract

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. 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.

PO‐322 exerts potent immunosuppressive effects in vitro and in vivo by selectively inhibiting SGK1 activity

“…Fluos-labelled Annexin V and PI dual staining kit (Roche, Indianapolis, IN, USA) was used to assess the cell apoptosis following the protocol F I G U R E 1 Chemical structure of oxazole derivatives and analysed by flow cytometry (Acurri C6) as previously described (Luo et al, 2019).…”

“…In addition, oxazole derivatives exhibit anti‐inflammatory activity by inhibiting GSK3β (Zhao et al, ), MAPK p38α (Kalgutkar et al, ), and COX‐2 and COX‐1 enzyme activities (Hashimoto, Imamura, Haruta, & Wakitani, ). Recently, we found an oxazole derivative, PO‐296, that could inhibit T‐cell proliferation through the JAK3/STAT5 signalling pathway (Luo et al, ). However, the immunosuppressive activity of oxazole derivatives through SGK1 inhibition has not been reported previously.…”

Crystal structure and cytotoxic activity of Cu(ii) complexes with bis-benzoxazolylhydrazone of 2,6-diacetylpyridine

“…It is known that compounds containing a benzoxazole fragment have possessed variety types of biological activity: anticancer, 30–36 analgesic, 37,38 antimicrobial, immunomodulatory, antituberculosis, etc. 39–50 Hydrazones based on hydrazinobenzoxazole and their complexes are practically not described in the literature, but the available examples of these compounds also exhibit anticancer properties.…”