8-[3,5-Difluoro-4-(4-morpholinylmethyl)phenyl]-2-[1-(4-piperidinyl)-1H-pyrazol-4-yl]quinoxaline dihydrochloride Chemical Properties

storage temp. 

Store at -20°C

solubility 

DMF: 20 mg/ml; DMSO: 25 mg/ml; Ethanol: 1 mg/ml; PBS (pH 7.2): 10 mg/ml

form 

A crystalline solid

color 

Light yellow to yellow

8-[3,5-Difluoro-4-(4-morpholinylmethyl)phenyl]-2-[1-(4-piperidinyl)-1H-pyrazol-4-yl]quinoxaline dihydrochloride Usage And Synthesis

Description

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. A point mutation of JAK2, V617F, activates signaling through STAT5 and drives certain forms of cancer. 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. 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. NVP-BSK805 suppresses recombinant human erythropoietin-induced polycythemia and extramedullary erythropoiesis in mice and rats. NVP-BSK805 can be used to study the molecular mechanisms involved in JAK2^V617F signaling in cells.

Uses

NVP-BSK805 dihydrochloride is an ATP-competitive JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively[1].

in vivo

IC 50

JAK2 JH1: 0.48 nM (IC₅₀); FL JAK2 V617F: 0.56 nM (IC₅₀); FL JAK2 wt: 0.58 nM (IC₅₀); TYK2 JH1: 10.76 nM (IC₅₀); JAK3 JH1: 18.68 nM (IC₅₀); JAK1 JH1: 31.63 nM (IC₅₀)

References

[1] Baffert F, et al. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010 Jul;9(7):1945-55. DOI:10.1158/1535-7163.MCT-10-0053
[2] Cheon JH, et al. The JAK2 inhibitors CEP-33779 and NVP-BSK805 have high P-gp inhibitory activity and sensitize drug-resistant cancer cells to vincristine. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1176-1182. DOI:10.1016/j.bbrc.2017.06.178

8-[3,5-Difluoro-4-(4-morpholinylmethyl)phenyl]-2-[1-(4-piperidinyl)-1H-pyrazol-4-yl]quinoxaline dihydrochloride(1942919-79-0)Related Product Information

• NVP-CGM097
• CEP-28122 monomesilate hydrochloride salt
• CEP-28122
• NVP-BSK805