A dual inhibitor of Syk and JAKs
Cerdulatinib is a dual inhibitor of spleen tyrosine kinase (Syk) and Janus kinases (JAK; IC50s = 32, 12, 6, 8, and 0.5 nM for Syk, JAK1, JAK2, JAK3, and TYK2, respectively) and also exhibits nanomolar inhibition of other kinases.1 Syk is involved in the B cell receptor (BCR) pathway, and cerdulatinib inhibits downstream Syk-mediated signaling of ERK Y204 phosphorylation (IC50 = 0.5 μM), upregulates cell surface expression of CD69 (IC50 = 0.11 μM), and inhibits FcεRI-mediated basophil degranulation (IC50 = 0.12 μM).1 JAK is involved in JAK-STAT regulation of cytokine receptors. Cerdulatinib inhibits STAT3, STAT5, and STAT6 phosphorylation by interleukin-activated JAK1/3 with IC50 values ranging from 0.16 to 1 μM.1 Cerdulatinib disrupts JAK1/3-mediated signaling more selectively than JAK2 signaling (IC50 > 4 μM).1 Cerdulatinib displays potent antitumor activity against ABC and GCB types of diffuse large B cell lymphoma (DLBCL) by inducing apoptosis via caspase-2 and poly(ADP-ribose) polymerase (PARP) cleavage.2 Cerdulatinib exhibits IC50 values ranging from 0.05 to 2.1 μM against a panel of DLBCL tumor cell lines.2
1.Coffey, G., Betz, A., DeGuzman, F., et al.The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancerJ. Pharmacol. Exp. Ther.351(3)538-548(2014) 2.Ma, J., Xing, W., Coffey, G., et al.Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphomaOncotarget6(41)43881-43896(2015)
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