NVP-BSK805

• CAT Number: I000383
• CAS Number: 1092499-93-8
• Molecular Formula: C27H28F2N6O
• Molecular Weight: 490.55
• Purity: ≥95%
• Target: JAK
• Solubility: DMSO 67 mg/mL; Water <1 mg/mL; Ethanol 7 mg/mL
• Storage: Store at -20°C
• IC50: 0.48 ± 0.02 nM (JAK2 JH1); 0.58 ± 0.03 nM (FL JAK2 wt) [1]

NVP-BSK805 is a potent and selective ATP-competitive JAK2 inhibitor with IC50 of 0.5 nM; >20-fold selectivity towards JAK1, JAK3 and TYK2.IC50 Value: 0.48 ± 0.02 nM (JAK2 JH1); 0.58 ± 0.03 nM (FL JAK2 wt) [1]Target: JAK2in vitro: NVP-BSK805 is found to potently inhibit JAK2, whereas displaying more than 20-fold selectivity towards JAK1, JAK3, and TYK2. NVP-BSK805 causes half-maximal inhibition of full-length JAK2V617F and JAK2 wild-type enzymes at 0.5 nM. NVP-BSK805 blocks the growth of JAK2V617F cells (Ba/F3) and induces apoptosis with a GI50 at concentrations ＜100 nM. As constitutive STAT5 phosphorylation in dependent on JAK2, NVP-BSK805 is found to potently suppress STAT5 phophorylation at ≥ 100 nM concentrations in the JAK2 V617F -mutant cell lines, like MB-02. Incubation of SET-2 cells with 150 nM and 1μM 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. These results are evidenced by the detection of cleaved PARP, reduced Bcl-xL expression, and a strong increase in the number of cells with less than 2N DNA content [1]. NVP-BSK805 triggered cell death requires activation of caspase cascades and is overcome by caspase inhibition in both SET-2 and MB-02 cells. NVP-BSK805 modulates the post-translational modification of Bim and levels of Mcl-1 in JAK2V617F cells, SET-2 and MB-02 cells [2].in vivo: Oral bioavailability of NVP-BSK805 in mice is estimated to be 45%, while it is 50% in rats. Oral administration of NVP-BSK805 at 150 mg/kg suppresses STAT5 phosphorylation, splenomegaly, and leukemic cell spreading in a Ba/F3 JAK2V617F cell–driven mouse model. NVP-BSK805 suppresses rhEpo-induced STAT5 phosphorylation as well as rhEpo-mediated polycythemia and splenomegaly in BALB/c mice at doses of 25, 50, and 100 mg/kg orally [1].

Reference

1:Effects of Jak2 type 1 inhibitors NVP-BSK805 and NVP-BVB808 on Jak2 mutation-positive and Bcr-Abl-positive cell lines. Ringel F, Kaeda J, Schwarz M, Oberender C, Grille P, Dörken B, Marque F, Manley PW, Radimerski T, le Coutre P.Acta Haematol. 2014;132(1):75-86. doi: 10.1159/000356784. Epub 2014 Jan 31. PMID: 24504330 2:Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Baffert F, Régnier CH, De Pover A, Pissot-Soldermann C, Tavares GA, Blasco F, Brueggen J, Chène P, Drueckes P, Erdmann D, Furet P, Gerspacher M, Lang M, Ledieu D, Nolan L, Ruetz S, Trappe J, Vangrevelinghe E, Wartmann M, Wyder L, Hofmann F, Radimerski T.Mol Cancer Ther. 2010 Jul;9(7):1945-55. doi: 10.1158/1535-7163.MCT-10-0053. Epub 2010 Jun 29. PMID: 20587663 Free Article