A cell-permeable, orally bioavailable pyrimidinediamino compound with anti-inflammatory and anti-tumor properties. Acts as a potent, reversible and ATP-competitive inhibitor of Syk kinase (IC₅₀ = 41 nM; K_i = 30 nM). Exhibits high selectivity over a broad panel of other protein kinases (˜300 nM), ion channels, and enzymes. Blocks Syk-dependent FcR-mediated activation of monocytes/macrophages, and neutrophils and inhibits Anti-IgE-mediated degranulation in cultured human mast cells (EC₅₀ = 56 nM as measured by tryptase release). At higher concentrations, it is shown to block adenosine A3 receptors, adenosine transporter, and monoamine transporter (IC₅₀ = 81 nM, 1.84 µM, and 2.74 µM, respectively), and Flt3 autophosphorylation. Shown to reduce immune complex-mediated inflammation in murine models (˜10 mg/kg) and diminish airway hyper-responsiveness in asthma models.

Cell permeable: yes

Primary Target
Syk kinase

Reversible: yes

Packaged under inert gas

Friedberg, J.W., et al. 2010. Blood115, 2578.

Young, R.M., et al. 2009. Blood113, 2508.
Young, R.M., et al. 2009. Blood113, 2508.

Chen, L., et al. 2008. Blood111, 2230.

Braselmann, S., et al. 2006. J. Pharmacol. Exp. Ther.319, 998.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)