NVP-BSK805 (dihydrochloride)

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]. IC50 & Target: IC50: 0.48 nM (JAK2 JH1), 31.63 nM (JAK1 JH1), 18.68 nM (JAK3 JH1), 10.76 nM (TYK2 JH1), 0.56 nM (FL JAK2 V617F), 0.58 nM (FL JAK2 wt)^[1] In Vitro: 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 K_i of 0.43 ± 0.02 nM. NVP-BSK805 suppresses the growth of JAK2^V617F-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 JAK2^V617F-mutant cell lines^[1].
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^[2].
In Vivo: NVP-BSK805 (BSK805 dihydrochloride; 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 (50, 75, and 100 mg/kg, p.o.) also suppresses rhEpo-mediated polycythemia and splenomegaly in BALB/c mice^[1].