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| | 8-[3,5-Difluoro-4-(4-morpholinylmethyl)phenyl]-2-[1-(4-piperidinyl)-1H-pyrazol-4-yl]quinoxaline dihydrochloride Basic information |
| | 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 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. 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. 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 JAK2V617F 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 | NVP-BSK805 (BSK805 dihydrochloride; 150 mg/kg, p.o.) blocks STAT5 phosphorylation, splenomegaly, and leukemic cell spreading in a Ba/F3 JAK2V617F cell-driven mouse model[1].
NVP-BSK805 (50, 75, and 100 mg/kg, p.o.) also suppresses rhEpo-mediated polycythemia and splenomegaly in BALB/c mice[1].
| | 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 Preparation Products And Raw materials |
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