NVP-BSK805

Research use only, not for human use.

A potent, selective and ATP-competitive inhibitor of JAK2(V617F) and wt JAK2 (IC50=0.5 nM).

A potent, selective and ATP-competitive inhibitor of JAK2(V617F) and wt JAK2 (IC50=0.5 nM); displays >20-fold selectivity towards JAK1, JAK3, TYK2 and excellent selectivity in broader kinase profiling; blunts constitutive STAT5 phosphorylation in JAK2(V617F)-bearing cells; exhibits good oral bioavailability and a long half-life.

NVP-BSK805 (BSK 805) 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 (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 (BSK 805; 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.

BSK 805 | BSK-805 | BSK805 | NVP-BSK 805

Angiogenesis

JAK

JAK1|JAK2|JAK3|Tyk2|JAK2JH1|FLJAK2V617F|FLJAK2wt|TYK2JH1|JAK3JH1|JAK1JH1

Cancer

——

1092499-93-8

490.5476

C27H28F2N6O

>98% (HPLC)

10 mM in DMSO

FC1=C(CN2CCOCC2)C(F)=CC(C3=C4N=C(C5=CN(C6CCNCC6)N=C5)C=NC4=CC=C3)=C1

Quinoxaline, 8-[3,5-difluoro-4-(4-morpholinylmethyl)phenyl]-2-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-

(-20℃)

With Ice Pack

≥ 2 years