产品描述:
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.{34576} 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).{34576} 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.{34576} Cerdulatinib disrupts JAK1/3-mediated signaling more selectively than JAK2 signaling (IC50 > 4 μM).{34576} 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.{34577} Cerdulatinib exhibits IC50 values ranging from 0.05 to 2.1 μM against a panel of DLBCL tumor cell lines.{34577}