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.

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