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Purity: ≥98%
NVP-BSK805 2HCl (BSK805), the dihydrochloride salt of NVP-BSK805, is a novel, potent, selective and ATP-competitive JAK2 (Janus kinase) inhibitor with potential antitumor activity. It inhibits JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1 with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM, respectively. NVP-BSK 805 shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy.
ln Vitro |
NVP-BSK805 diHClide (BSK805 diHClide) is a JAK2 inhibitor that has IC50 values for JAK2 JH1 (JAK Homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1 of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM, respectively. Full-length wild-type JAK2 (FL JAK2 wt) and FL JAK2 V617F are both inhibited by NVP-BSK805, with IC50 values of 0.58 ± 0.03 and 0.56 ± 0.04 nM, respectively. NVP-BSK805 has a cumulative Ki of 0.43 ± 0.02 nM, making it ATP competitive. Acute myeloid leukemia cell lines carrying JAK2V617F are inhibited from growing by NVP-BSK805 at GI50 <100 nM. In JAK2V617F mutant cell lines, NVP-BSK805 shows better inhibition of JAK2 than JAK1 and JAK3, and it blocks STAT5 phosphorylation at doses ≥100 nM [1]. Dihydrochloride of NVP-BSK805 (5 μM) increases the inhibitory action of P-gp. Drug-resistant KBV20C cancer cells are more sensitive to 10 μM VIC therapy when treated with NVP-BSK805, and this effect is more potent than when treated with a 5 μM dosage [2].
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ln Vivo |
In a Ba/F3 JAK2V617F cell-driven mouse model, NVP-BSK805 (BSK805 dihydrochloride; 150 mg/kg, po) inhibits splenomegaly, leukemic cell spreading, and STAT5 phosphorylation[1]. In BALB/c mice, NVP-BSK805 (50, 75, and 100 mg /kg, po) also reduces splenomegaly and rhEpo-mediated polycythemia[1].
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Animal Protocol |
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References |
[1]. Baffert F, et al. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010 Jul;9(7):1945-55.
[2]. Cheon JH, et al. The JAK2 inhibitors CEP-33779 and NVP-BSK805 have high P-gp inhibitory activity and sensitize drug-resistant cancer cells to vincristine. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1176-1182 |
Molecular Formula |
C27H28F2N6O.2HCL
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Molecular Weight |
563.47
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CAS # |
1942919-79-0
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Related CAS # |
NVP-BSK805;1092499-93-8;NVP-BSK805 trihydrochloride;2320258-95-3
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SMILES |
Cl.Cl.FC1C=C(C=C(C=1CN1CCOCC1)F)C1C=CC=C2C=1N=C(C=N2)C1C=NN(C=1)C1CCNCC1
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Synonyms |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7747 mL | 8.8736 mL | 17.7472 mL | |
5 mM | 0.3549 mL | 1.7747 mL | 3.5494 mL | |
10 mM | 0.1775 mL | 0.8874 mL | 1.7747 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Caspase inhibition rescues JAK2V617F mutant cells from the apoptotic and anti-proliferative effects of the JAK2 inhibitor NVP-BSK805.BMC Cancer.2011 Jan 19;11:24. td> |
Bad and Bim depletion in JAK2V617F mutant SET-2 cells suppress NVP-BSK805-induced apoptosis.BMC Cancer.2011 Jan 19;11:24. td> |
Analysis of Bim phosphorylation in JAK2V617F mutant SET-2 cells.BMC Cancer.2011 Jan 19;11:24. td> |