NVP-BSK805 2HCl is a potent and selective ATP-competitive inhibitor of JAK2.

NVP-BSK805 potently inhibited JAK2, displaying more than 20-fold selectivity towards JAK1, JAK3, and TYK2. In an internal kinase panel, NVP-BSK805 showed potent inhibition of JAK2, along with good selectivity towards the other three JAK family members, indicating the fair selectivity against other kinases. NVP-BSK805 is an ATP-competitive inhibitor (Ki: 0.43 ± 0.02 nmol/L). In Ba/F3 cell-based assays of JAK2V617F dependency and a panel of JAK2V617F-bearing acute myeloid leukemia cell lines derived from patients with a history of cMPNs, NVP-BSK805 exhibited half-maximal growth inhibition (GI50) at concentrations< 100 nmol/L. In K-562 cells, NVP-BSK805 suppressed growth (GI50: 1.5 μmol/L). In CMK cells, the GI50value of NVP-BSK805 was about 2 μmol/L. Incubation of SET-2 cells with 150 nM and 1 μM of NVP-BSK805, which corresponds to concentration yielding 75% and 95% growth inhibition, respectively, for 24, 48, and 72 hours lead to concentration- and time-dependent induction of apoptosis. In both SET-2 and MB-02 cells, NVP-BSK805 triggered cell death required activation of caspase cascades and was overcome by caspase inhibition. NVP-BSK805 modulated the post-translational modification of Bim and levels of Mcl-1 in JAK2V617F cells, SET-2, and MB-02 cells[1][3].

The oral bioavailability of NVP-BSK805 in mice was estimated to be 45%, while 50% in rats. In a Ba/F3 JAK2V617F cell-driven mouse model, Oral administration of NVP-BSK805 (150 mg/kg) suppressed STAT5 phosphorylation, splenomegaly, and leukemic cell spreading. In BALB/c mice, NVP-BSK805 suppressedrhEpo-induced STAT5 phosphorylation as well as rhEpo-mediated polycythemia and splenomegaly at doses of 25, 50, and 100 mg/kg orally [1].

T23096

C27H28F2N6O·2HCl

563.47

NVP-BSK805 2HCl;NVP-BSK805 2HCl (1092499-93-8 free base)

H2O:<1 mgml
DMSO:≥214 mg/mL
Ethanol:≥8.03 mg/mL,with ultrasonic and warmingmg
Powder: -20°C for 3 years
In solvent: -80°C for 2 years