NVP-BSK805 dihydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

NVP-BSK805 diHClide 是一种有效的选择性 JAK2 抑制剂，对 JAK2、TYK2、JAK3 和 JAK1 的 IC50 分别为 0.5 nM、10.76 nM、18.68 nM 和 31.63 nM。

NVP-BSK805 dihydrochloride is an effective and selective inhibitor of JAK2 with IC50s of 0.5 nM, 10.76 nM, 18.68 nM, and 31.63 nM for JAK2, TYK2, JAK3, and JAK1.(In Vitro):In JAK2V617F-mutated cells, NVP-BSK805 dihydrochloride (100 nM) significantly inhibits the phosphorylation of STAT5 like MB-02. Incubation of SET-2 cells with NVP-BSK805 dihydrochloride (150 nM and 1 μM) inhibits cell growth in a concentration- and time-dependent manner by 75% and 95%, respectively. In JAK2 (V617F), SET-2, and MB-02 cells, NVP-BSK805 dihydrochloride regulates the post-translational modification of Bim and the level of Mcl-1.(In Vivo):The utilization efficiency of oral NVP-BSK805 dihydrochloride biopharmaceuticals was estimated to be 45% in mice and 50% in rats. Oral administration of 150 mg/kg NVP-BSK805 dihydrochloride to a mouse model harboring Ba/F3 JAK2V617F cells inhibited STAT5 phosphorylation, splenomegaly, and leukemia cell proliferation. Oral administration of 25, 50 and 100 mg/kg of NVP-BSK805 dihydrochloride to BALB/c mice inhibited rhEpo-induced STAT5 phosphorylation and rhEpo-regulated erythrocytosis and splenomegaly.

NVP-BSK805 dihydrochloride (BSK805 dihydrochloride) is a 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. NVP-BSK805 inhibits the full-length wild-type JAK2 (FL JAK2 wt) and FL JAK2 V617F activity, with IC50s of 0.58 ± 0.03 and 0.56 ± 0.04 nM. NVP-BSK805 is ATP-competitive, with aclculated Ki of 0.43 ± 0.02 nM. NVP-BSK805 suppresses the growth of JAK2V617F-bearing acute myeloid leukemia cell lines with GI50 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. NVP-BSK805 dihydrochloride (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.

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.NVP-BSK805 (50, 75, and 100 mg/kg, p.o.) also suppresses rhEpo-mediated polycythemia and splenomegaly in BALB/c mice.

NVP-BSK805 2HCl | BSK805 | BSK 805 | NVP-BSK805 (dihydrochloride)

Angiogenesis

JAK

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1942919-79-0

563.47

C27H30Cl2F2N6O

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (88.74 mM)

FC1=C(CN2CCOCC2)C(F)=CC(C3=CC=CC4=C3N=C(C5=CN(C6CCNCC6)N=C5)C=N4)=C1.Cl.Cl

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(-20℃)

With Ice Pack

≥ 2 years