NVP-BSK805 trihydrochloride is a potent ATP-competitive inhibitor of JAK2, exhibiting IC50 values of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM against JAK2 JH1, JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively.

JAK2 (V617F):0.56 nM (IC50), JAK1 JH1:31.68 nM (IC50), TYK2 JH1:18.68 nM (IC50), FL JAK2 (WT):0.58 nM (IC50), JAK2 JH1:0.48 nM (IC50)

NVP-BSK805 trihydrochloride (BSK 805) is a JAK2 inhibitor, with IC 50 s 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 trihydrochloride inhibits the full-length wild-type JAK2 (FL JAK2 wt) and FL JAK2 V617F activity, with IC 50 s of 0.58 ± 0.03 and 0.56 ± 0.04 nM. NVP-BSK805 trihydrochloride is ATP-competitive, with aclculated K i of 0.43 ± 0.02 nM. NVP-BSK805 trihydrochloride suppresses the growth of JAK2 V617F -bearing acute myeloid leukemia cell lines with GI 50 of <100 nM. NVP-BSK805 trihydrochloride blocks the STAT5 phosphorylation at ≥100 nM concentrations, and shows a bias for JAK2 over JAK1 and JAK3 inhibition in the JAK2 V617F -mutant cell lines[1]. NVP-BSK805 trihydrochloride (5 μM) improves P-gp inhibitory activity. NVP-BSK805 trihydrochloride 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].

NVP-BSK805 trihydrochloride (BSK 805; 150 mg/kg, p.o.) blocks STAT5 phosphorylation, splenomegaly, and leukemic cell spreading in a Ba/F3 JAK2 V617F cell-driven mouse model[1]. NVP-BSK805 trihydrochloride (50, 75, and 100 mg/kg, p.o.) also suppresses rhEpo-mediated polycythemia and splenomegaly in BALB/c mice[1].