Molecular Formula | C28H29FN6O8S |
Molar Mass | 628.6286632 |
In vitro study | R406 strongly inhibits Immunoglobulin E (IgE) and IgG-regulated receptor signaling activity. R406 inhibits IgE antibody-induced production and release of LTC4, cytokines, and chemokines, including TNFα, IL-8, and GM-CSF. R406 inhibits activation of T-cell Syk substrate linker protein in mast cells and phosphorylation of B- cell linker protein/SLP65 in B- cells. R406 binds to the ATP-binding pocket of Syk, which is a competitive inhibitor of ATP, and inhibits the kinase activity of Syk, with K I of 30 nM. R406 blocks Syk-dependent FcR regulatory activity in monocytes/macrophages and neutrophils and BCR regulatory activity in B lymphocytes. 406 significantly induced apoptosis of chronic lymphocytic leukemia (CCL) cells, and blocked the secretion of CCL3 and ccl4. R406 effectively inhibits platelet signaling and inhibits the function of plasma formed by Fc gamma RIIA cross-binding in patients using specific antibodies or HIT. |
In vivo study | In mice that had been prophylactically treated, a positive Arthus reaction was performed, and 5 mg/kg R406 induced 86% of the murine skin lesions. R406 acts on the antibody-induced arthritis mouse model and also effectively inhibits inflammation. During the autoimmune reaction, R406 did not affect the function of macrophages and neutrophils, and the immunotoxicity was the lowest. |