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.

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

NVP-BSK805 trihydrochloride (BSK 805) effectively inhibits JAK2 with an IC50 of 0.48 nM for JAK2 JH1 and also targets JAK1, JAK3, and TYK2. It inhibits both wild-type and V617F mutant JAK2 with an IC50 of 0.57 nM, demonstrating ATP-competitive inhibition with a Ki of 0.43 nM. In acute myeloid leukemia cells with the JAK2 V617F mutation, it significantly suppresses growth at concentrations below 100 nM and obstructs STAT5 phosphorylation at concentrations of 100 nM or higher. At 5 μM, it enhances P-gp inhibitory activity and at 10 μM, increases the sensitivity of drug-resistant KBV20C cancer cells to VIC treatment, outperforming lower doses in efficacy.

NVP-BSK805 trihydrochloride (BSK 805; 150 mg/kg, p.o.) effectively inhibits STAT5 phosphorylation, reduces splenomegaly, and prevents leukemic cell dissemination in a Ba/F3 JAK2 V617F cell-driven mouse model[1]. Lower doses (50, 75, and 100 mg/kg, p.o.) also diminish rhEpo-induced polycythemia and splenomegaly in BALB/c mice[1].