NVP-BSK805 can potently suppress JAK2 with IC50 of 0.5 nM, and displays more than 20-fold selectivity towards JAK1, JAK3, and TYK2. NVP-BSK805 shows inhibition to causes JAK2V617F and JAK2 wild-type with IC50 of 0.5 nM. For cell lines, NVP-BSK805 inhibt JAK2V617F cells (Ba/F3) growth and induce cell apoptosis. NVP-BSK805 also can potently inhibit STAT5. By inducing activation of caspase cascades, NVP-BSK805 triggered cell death.
In vivo
In a Ba/F3 JAK2V617F cell driven mouse model, oral administration of NVP-BSK805(150 mg/kg) shows suppression to STAT5 phosphorylation, splenomegaly, and leukemic cell spreading.