R406

Syk inhibitor

R406 (the active metabolite of Fostamatinib) is a specific, ATP-competitive inhibitor of spleen tyrosine kinase (Syk), which plays a key role in the signaling of activating Fc receptors and the B-cell receptor.

R406 was shown to potently inhibit IgE- and IgG-mediated activation of Fc receptor signaling and to reduce inflammation in animal models of arthritis [1].

In cancers characterized by over-expression of Syk, R406 treatment induces the activation of caspase leading to significant apoptosis [2, 3]. Syk also activates the NLRP3 inflammasome [4]. Inhibition of Syk with R406 selectively abrogates inflammasome activation by C. albicans but not by inflammasome activators such as the bacterial toxin nigericin [4].

References:

1. Braselmann S. et al., 2006. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 319(3):998-1008.
2. Chen L. et al., 2008. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood. 111(4):2230-7.
3. Zhang J. et al., 2012. A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature. 481(7381):329-34.
4. Gross O. et al., 2009. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 459, 433-436.

Specifications

CAS number: 841290-80-0

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

Formula: C₂₂H₂₃FN₆O₅

Molecular weight: 470.45

Solubility: 20 mg/ml (42 mM) in DMSO

Purity: >97% (UHPLC)

Quality control:

• The absence of bacterial contamination (e.g. endotoxins, peptidoglycans) is controlled using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.

Contents

R406 provided as a lyophilized powder.

• 2 mg R406

R406 is shipped at room temperature.

Store lyophilized product at -20˚C for up to 2 years.