Molecular Formula | C22H23FN6O5 |
Molar Mass | 470.45 |
Density | 1.358±0.06 g/cm3(Predicted) |
Melting Point | 182-184°C |
Solubility | DMSO (Slightly), Methanol (Slightly) |
Appearance | Solid |
Color | Off-White to Light Grey |
pKa | 10.63±0.40(Predicted) |
Storage Condition | Refrigerator |
Use | R406 is an effective Syk inhibitor with IC50 of 41 nM, which has a strong inhibitory effect on Syk, but does not inhibit Lyn, and its effect on Flt3 is 5 times weaker. Phase 1. |
In vitro study | R406 is an ATP competitive Syk inhibitor with a K I of 30 nM. R406 selectively inhibits Syk-dependent signaling pathways in different cells, with EC50 ranging from 33 nM to 171 nM, which is much more effective than acting on Syk-independent pathways. R406 acts on a variety of diffuse giant cell lymphoma and inhibits cell proliferation. EC50 is 0.8 μm to 8.1 μm. Treatment of DLBCL cell lines with 1 μm or 4 μm R406 induced activation of caspases 9 and 3, but not caspase 8, resulting in apoptosis in most of the cells. Pretreatment of R406 B- cell receptor (BCR)-crosslinked DLBCLs sensitive to R406 completely inhibited SYK525/526 phosphorylation and BLNK-dependent SYK phosphorylation. R406 effectively reduced the level of MMP-9 mRNA, treated for 24 and 48 hours, 2.8 and 4.3 times lower than the control group, respectively, and reduced the invasion ability of RL cells. |
In vivo study | R406 is effective in animal models of a variety of immune system disorders. R406 oral administration of immune complex-induced inflammatory responses in mice significantly inhibited the reverse passive Arthus response in the skin, treated at doses of 1 mg/kg and 5 mg/kg, compared with the control group, the inhibition was 72% and 86%, respectively. R406 Treatment of mice treated with collagen antibodies at a dose of 10 mg/kg significantly reduced inflammation and swelling, reduced progressive arthritis to a lower level, and delayed onset, and it acts on the mouse model of K/BxN serum transfer, reducing clinical arthritis by 50%. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.591 ml | 7.954 ml | 15.908 ml |
5 mM | 0.318 ml | 1.591 ml | 3.182 ml |
10 mM | 0.159 ml | 0.795 ml | 1.591 ml |
5 mM | 0.032 ml | 0.159 ml | 0.318 ml |