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| Targets |
The primary molecular target of NVP-BSK805 is Janus kinase 2 (JAK2), a member of the JAK family of non-receptor tyrosine kinases. JAK2 plays a critical role in cytokine signaling, particularly in the erythropoietin and thrombopoietin signaling pathways. NVP-BSK805 is an ATP-competitive inhibitor that binds to the ATP-binding site of JAK2, preventing its activation and downstream signaling. The compound shows high selectivity for JAK2 over other JAK family members, with IC50 values of 31.63 nM for JAK1, 18.68 nM for JAK3, and 10.76 nM for TYK2. This selectivity makes it a valuable tool for studying JAK2-specific signaling pathways.
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| ln Vitro |
With IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively, NVP-BSK805 (BSK 805) is a JAK2 inhibitor. Full-length wild-type JAK2 (FL JAK2 wt) and FL JAK2 V617F activity are inhibited by NVP-BSK805, with IC50s of 0.58 ± 0.03 and 0.56 ± 0.04 nM, respectively. ATP-competitive, NVP-BSK805 has an estimated Ki of 0.43 ± 0.02 nM. JAK2V617F-bearing acute myeloid leukemia cell lines with GI50 of less than 100 nM are inhibited in proliferation by NVP-BSK805. In the JAK2V617F-mutant cell lines, NVP-BSK805 exhibits a bias for JAK2 over JAK1 and JAK3 inhibition and inhibits STAT5 phosphorylation at ≥100 nM concentrations[1]. NVP-BSK805 (5 μM) enhances the inhibitory action of P-gp. Drug-resistant KBV20C cancer cells become more sensitive to VIC therapy when treated with NVP-BSK805 at a dose of 10 μM; this result outperforms that of a 5 μM dose[2].
In vitro studies demonstrate that NVP-BSK805 is a potent and selective JAK2 inhibitor with an IC50 of 0.48 nM. It shows >20-fold selectivity for JAK2 over JAK1, JAK3, and TYK2. The compound inhibits JAK2-mediated signaling, including STAT5 phosphorylation, in cellular assays. It effectively inhibits recombinant human erythropoietin-induced polycythemia and extramedullary hematopoiesis in mice and rats. The compound's potency and selectivity make it a valuable tool for studying JAK2 biology and for the development of JAK2-targeted therapies for myeloproliferative neoplasms and other JAK2-driven diseases. |
| ln Vivo |
In a mouse model driven by Ba/F3 JAK2V617F cells, NVP-BSK805 (BSK 805; 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].
In vivo studies of NVP-BSK805 have demonstrated its efficacy in animal models of myeloproliferative neoplasms. The compound effectively inhibits recombinant human erythropoietin-induced polycythemia and extramedullary hematopoiesis in mice and rats. In vivo protocols typically involve administration of NVP-BSK805 via oral gavage or intraperitoneal injection at doses determined from pharmacokinetic studies. Endpoints include assessment of hematocrit levels, spleen size, JAK2-STAT5 signaling, and histopathological examination. The compound's efficacy and selectivity have been validated in preclinical studies. |
| Enzyme Assay |
For JAK2 kinase assays, the enzymatic activity of recombinant JAK2 is measured using a radiometric or fluorescence-based assay. Purified JAK2 enzyme is incubated with varying concentrations of NVP-BSK805 (typically 0.0001-10 µM) in reaction buffer containing 50 mM HEPES (pH 7.5), 10 mM MgCl₂, 1 mM DTT, and 0.01% Triton X-100 at 30°C. The reaction is initiated by the addition of ATP and a peptide substrate, and incubated for 30-60 minutes. IC50 values are calculated from dose-response curves. For selectivity profiling, the compound is tested against JAK1, JAK3, TYK2, and other kinases.
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| Cell Assay |
For cellular studies, cells expressing JAK2 (e.g., HEL, SET-2, or Ba/F3 cells expressing JAK2 mutants) are cultured in appropriate medium (RPMI-1640) with 10% FBS and antibiotics. Cells are seeded in 6-well or 96-well plates. NVP-BSK805 is dissolved in DMSO and diluted in culture medium to final concentrations (typically 0.001-10 µM). Cells are treated for 1-4 hours. Cells are lysed in RIPA buffer with protease and phosphatase inhibitors. JAK2 signaling is assessed by measuring phosphorylation of STAT5 (p-STAT5) by Western blot or ELISA. Cell viability is assessed by MTT or CellTiter-Glo assays after 48-72 hours of treatment. Apoptosis is assessed by Annexin V/PI staining.
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| Animal Protocol |
For in vivo efficacy studies, animal models of myeloproliferative neoplasms (e.g., JAK2V617F transgenic mice or xenograft models) are used. NVP-BSK805 is formulated in vehicle and administered orally or intraperitoneally at doses of 1-50 mg/kg, typically once or twice daily for 2-4 weeks. Hematocrit levels, spleen size, and white blood cell counts are monitored. JAK2-STAT5 signaling is assessed in blood and tissues by Western blot. Histopathological examination of spleen and bone marrow is performed. For pharmacokinetic studies, blood samples are collected at various time points for compound quantification by LC-MS.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for NVP-BSK805 indicate that it is orally bioavailable. The compound has favorable pharmacokinetic properties, including moderate half-life and good tissue distribution. Its pharmacokinetic profile supports once- or twice-daily dosing in preclinical studies. However, detailed pharmacokinetic parameters are not extensively reported in the public domain.
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| Toxicity/Toxicokinetics |
Toxicological data for NVP-BSK805 are limited, as the compound is a research tool. In preclinical studies, the compound has been shown to be well-tolerated at pharmacologically active doses. No acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. As with all research compounds, appropriate safety precautions should be taken when handling NVP-BSK805, including the use of personal protective equipment and work in a well-ventilated area.
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| References |
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| Additional Infomation |
NVP-BSK805 (CAS 1092499-93-8) is a potent and selective ATP-competitive JAK2 inhibitor with an IC50 of 0.48 nM. It was developed by Novartis as a research tool for myeloproliferative neoplasm studies. It has a molecular formula of C₂₇H₂₈F₂N₆O and a molecular weight of 490.55. The compound shows >20-fold selectivity for JAK2 over JAK1, JAK3, and TYK2. It inhibits erythropoietin-induced polycythemia in mice and rats. The compound is strictly for research use only.
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| Molecular Formula |
C27H28F2N6O-HCL
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| Molecular Weight |
527.01
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| CAS # |
1092499-93-8
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| Related CAS # |
NVP-BSK805 dihydrochloride;1942919-79-0;NVP-BSK805 trihydrochloride;2320258-95-3
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| Appearance |
Off-white to yellow solid powder
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| SMILES |
C1CNCCC1N2C=C(C=N2)C3=NC4=C(C=CC=C4N=C3)C5=CC(=C(C(=C5)F)CN6CCOCC6)F.Cl.Cl
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8975 mL | 9.4875 mL | 18.9750 mL | |
| 5 mM | 0.3795 mL | 1.8975 mL | 3.7950 mL | |
| 10 mM | 0.1897 mL | 0.9487 mL | 1.8975 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.
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