Janus-
associated kinases (JAKs) are cytoplasmic tyrosine kinases that are required for activating the signaling of certain cytokines and growth factor receptors. Many myeloproliferative diseases have been linked to a mutation in JAK2 where a switch from valine to phenylalanine occurs at the 617 position (V617F).
1 Furthermore, constitutive activation of the JAK2 signaling pathway is associated with aggressive adult T cell leukemia/lymphoma.
2 AZ 960 inhibits JAK2 with a K
i value of 0.45 nM
in vitro.
1 It can decrease STAT3/5 phosphorylation and inhibit cell proliferation in a SET-
2 human megakaryoblastic cell line that is heterozygous for the JAK2 V617F mutation with a GI
50 value of 33 nM.
1 AZ 960 can also induce apoptosis in human T cell lymophotropic virus type 1-
infected (IC
50 = ~1 μM), which corresponds to a downregulation of phosphorylated forms of JAK2 and Bcl-
2 family proteins.
2 
