NVP-BSK805-(BSK-805)-JAK-Inhibitor-MedChemExpress
NVP-BSK805Cat. No.:
HY-14722CAS No.:
1092499-93-8分?式:
C??H??F?N?O 分?量:
490.55作?靶点:
JAK 作?通路:
Epigenetics; JAK/STAT Signaling; Stem Cell/Wnt 储存?式:Please store the product under the recommended conditions in the COA.BIOLOGICAL ACTIVITY
?物活性NVP-BSK805 是?种 ATP 竞争性的 JAK2 抑制剂，对 JAK2 JH1 (JAK 同源 1)，JAK1 JH1，JAK3 JH1，和 TYK2 JH1 的 IC
50 值分别为 0.48 nM ，31.63 nM，18.68 nM 和 10.76 nM 。
IC?? & Target JAK2 JH1
0.48 nM (IC 50)
FL JAK2 V617F 0.56 nM (IC 50)FL JAK2 wt 0.58 nM (IC 50)TYK2 JH110.76 nM (IC 50)
JAK3 JH1
18.68 nM (IC 50)JAK1 JH131.63 nM (IC 50)体外研究NVP-BSK805 is a JAK2 inhibitor, with IC 50s 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. NVP-BSK805 inhibits the full-length wild-type JAK2 (FL
JAK2 wt) and FL JAK2 V617F activity, with IC 50s of 0.58 ± 0.03 and 0.56 ± 0.04 nM. NVP-BSK805 is ATP-competitive,
with aclculated K i of 0.43 ± 0.02 nM. NVP-BSK805 suppresses the growth of JAK2V617F -bearing acute myeloid
leukemia cell lines with GI 50 of <100 nM. NVP-BSK805 blocks the STAT5 phosphorylation at ≥100 nM concentrations,
and shows a bias for JAK2 over JAK1 and JAK3 inhibition in the JAK2V617F -mutant cell lines [1]. NVP-BSK805 (5 μM)
improves P-gp inhibitory activity. NVP-BSK805 increases sensitization of drug-resistant KBV20C cancer cells to VIC
treatment at 10 μM, and such an effect is more effective than a 5 μM dose [2].
体内研究NVP-BSK805 (150 mg/kg, p.o.) blocks STAT5 phosphorylation, splenomegaly, and leukemic cell spreading in a Ba/F3
JAK2V617F cell-driven mouse model. NVP-BSK805 (50, 75, and 100 mg/kg, p.o.) also suppresses rhEpo-mediated
polycythemia and splenomegaly in BALB/c mice [1].
PROTOCOL
Cell Assay [1]The antiproliferative activity of JAK2 inhibitors is determined by incubating cells for 72 hours (96 hours for MB-02
and MUTZ-8 cells ) with an 8-point concentration range of NVP-BSK805 and cell proliferation relative to NVP-
BSK805 is measured using the colorimetric WST-1 cell viability readout. Of each triplicate treatment, the mean is
calculated and these data are plotted in XLfit 4 to determine the half-maximal growth inhibition (GI 50) values [1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Product Data Sheet
Inhibitors ?Agonists ?Screening Libraries
Animal Administration [1]Mice[1]
Concomitantly with NVP-BSK805 treatment, female BALB/c mice receive daily s.c. injections (in 100 μL saline buffer) of 10 units of rhEpo for 4 consecutive days. Controls are injected corresponding volumes of saline buffer. Mice are sacrificed 24 hours after the final dose and total blood, spleen, and bone marrow are taken for further analysis. Animals are 8 to 10 weeks of age at treatment start (20-25 g body weight) and are kept under optimal hygienic conditions with free access to food and water[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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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.
[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.
McePdfHeight
Caution: Product has not been fully validated for medical applications. For research use only.
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Master of Small Molecules — 您?边的抑制剂?师
? Patent. US20180263995A1.