NVP-BSK805 dihydrochloride

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 JAK2^V617F 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 JAK2^V617F 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 JAK2^V617F 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)