5-Fluoro-2-[[(1S)-1-(4-fluorophenyl)ethyl]amino]-6-[(5-methyl-1H-pyrazol-3-yl)amino]-3-pyridinecarbonitrile

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). Furthermore, constitutive activation of the JAK2 signaling pathway is associated with aggressive adult T cell leukemia/lymphoma. AZ 960 inhibits JAK2 with a K_i value of 0.45 nM in vitro. 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 GI₅₀ value of 33 nM. AZ 960 can also induce apoptosis in human T cell lymophotropic virus type 1-infected (IC₅₀ = ~1 μM), which corresponds to a downregulation of phosphorylated forms of JAK2 and Bcl-2 family proteins.

AZ-960 Tyrosine Kinase inhibitor is useful for studying effects of the JAK2 Inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the Human JAK2 V617F Cell Line SET-2.

JAK2

JAK2: 0.45 nM (Ki); JAK2: <3 nM (IC₅₀); JAK3: 9 nM (IC₅₀)

[1] JOSEPH M GOZGIT. Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2.[J]. The Journal of Biological Chemistry, 2008, 283 47: 32334-32343. DOI: 10.1074/jbc.m803813200
[2] JING YANG. AZ960, a novel Jak2 inhibitor, induces growth arrest and apoptosis in adult T-cell leukemia cells.[J]. Molecular Cancer Therapeutics, 2010, 9 12: 3386-3395. DOI: 10.1158/1535-7163.mct-10-0416