NVP-BSK805 dihydrochloride

Biological Activity

NVP-BSK805 dihydrochloride is a potent and selective quinoxaline JAK2 inhibitor with IC50 values of 0.48, 0.56 and 0.58 nM for JAK2 JH1, FL JAK V617F and FL JAK2 wt respectively. Within the JAK family, NVP-BSK805 displays more than 20-fold selectivity towards JAK2 in vitro, as well as excellent selectivity in broader kinase profiling. The compound blunts constitutive STAT5 phosphorylation in JAK2(V617F)-bearing cells, with concomitant suppression of cell proliferation and induction of apoptosis. In vivo, NVP-BSK805 exhibited good oral bioavailability and a long half-life. The inhibitor was efficacious in suppressing leukemic cell spreading and splenomegaly in a Ba/F3 JAK2(V617F) cell-driven mouse mechanistic model. Furthermore, NVP-BSK805 potently suppressed recombinant human erythropoietin-induced polycythemia and extramedullary erythropoiesis in mice and rats.

Customer Product Validations & Biological Datas

	Source	Acta Haematol (2014). Figure 4. NVP-BSK805
	Method	Western blot
	Cell Lines	SET-2 and HEL cell line
	Concentrations	0.01, 0.05, 0.1, 0.5, 1.0 μM
	Incubation Time	24 h
	Results	The JAK2-positive cell line SET-2 showed suppression of STAT5a phosphorylation already at a concentration of 0.1 μ M of NVP-BSK805 and NVP-BVB808, whereas in HEL cells higher concentrations

Chemical Information

Molecular Weight	563.47
Formula	C27H28F2N6O.2HCl
CAS Number	1942919-79-0
Solubility (25°C)	DMSO 60 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.