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Cerdulatinib (PRT062070) is a potent and selective inhibitor of Syk and JAK.[1]

The JAK/STAT cascade, which has been implicated in hematopoiesis and cytokine signaling, is present in humans and flies. Worms. The SYK/ZAP70 kinases play an important role in human T and B cell signaling.[3]

Cerdulatinib can induce apoptosis via down-regulation of MCL1 protein and PARP cleavage. Through the inhibition of RB phosphorylation and down-regulation of cyclin E,the Cerdulatinib can also block G1/S transition and cause cell cycle arrest. Further analyses of the cell signaling activities showed that STAT3 phosphorylation was sensitive to inhibition by cerdulatinib in ABC cell lines while phosphorylation of SYK, PLCg2, AKT and ERK is reported to be sensitive to inhibition by cerdulatinib in GCB cell lines.[2]

Cerdulatinib is effective in rodent models of B-cell lymphoma and autoimmune disease and has exhibited anti-tumor activity in genetically diverse B-cell lymphoma cell lines and is more effective than Syk- or Jak- selective inhibitors alone.[1]

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