Description
R406 can inhibit syk with IC50 of 30 nM.
Storage
2 years at -20centigrade Powder
Molecular Formula
C22H23FN6O5.C6H6O3S
Chemical Name
6-(5-fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one benzenesulfonate
Solubility
DMSO 126 mg/mL Water
In vitro
As an ATP-competitive inhibitor, R406 can inhibit spleen tyrosine kinase (Syk) with Ki of 30nM. R406 inhibit spleen tyrosine kinase (Syk), which plays a key role in the signaling of activating Fc receptors and the B-cell receptor (BCR), by bounding to the ATP binding pocket of Syk. R406 inhibited phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 can block Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and BCR-mediated activation of B lymphocytes. R406 was selective as assessed using a large panel of Syk-independent cell-based assays representing both specific and general signaling pathways.R406 can also potently inhibit immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling with EC50 of 56-64 nM.
In vivo
R406 can block Syk, which is the key component of BCR signaling. And antigenic stimulation through the B-cell antigen receptor (BCR) is considered to promote the expansion of chronic lymphocytic leukemia (CLL) B cells. Researchers confirmed that R406 inhibited constitutive and BCR-induced activation of Syk, extracellular signal-regulated kinases, and AKT, and blocked BCR-induced calcium mobilization and blocked these BCR-dependent responses in CLL cells. Immunotoxicity Syk signaling plays critical roles in regulating the lymphohematopoietic system, but inhibition of Syk by R406 leads to minimal functional immunotoxicity notwithstanding its lymphocytopenic effect. Inhibition of Syk might not lead to unacceptable mechanism-based adverse effects.
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