Janus kinases (JAKs) are non-receptor tyrosine kinases that mediate signaling through cytokine receptors, often to members of the signal transducer and activator of transcription (STAT) family.1 A point mutation of JAK2, V617F, activates signaling through STAT5 and drives certain forms of cancer.2 NVP-BSK805 is a potent inhibitor of JAK2 that also inhibits the JAK2V617F mutant enzyme (IC50s for both enzymes ~ 0.5 nM). It displays at least 20-fold selectivity against other JAK enzymes and a panel of serine/threonine and tyrosine kinases.2 This ATP-competitive inhibitor is orally bioavailable and has a long half-life in vivo, suppressing leukemic cell spreading and splenomegaly in JAK2V617F cell-driven disease in mice.2 NVP-BSK805 suppresses recombinant human erythropoietin-induced polycythemia and extramedullary erythropoiesis in mice and rats.2 NVP-BSK805 can be used to study the molecular mechanisms involved in JAK2V617F signaling in cells.3
1.Yamaoka, K., Saharinen, P., Pesu, M., et al.The Janus kinases (Jaks)Genome Biol.5(12)253(2004) 2.Baffert, F., Régnier, C.H., De Pover, A., et al.Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805Mol. Cancer Ther.9(7)1945-1955(2010) 3.Rubert, J., Qian, Z., Andraos, R., et al.Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survivalBMC Cancer11:24(2011)