| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
JAK2 JH1 0.48 nM (IC50) FL JAK2 V617F 0.56 nM (IC50) FL JAK2 wt 0.58 nM (IC50) TYK2 JH1 10.76 nM (IC50) JAK3 JH1 18.68 nM (IC50) JAK1 JH1 31.63 nM (IC50)
JAK2 (Janus kinase 2). NVP-BSK805 is an ATP-competitive JAK2 inhibitor with IC50 values of 0.48 nM for JAK2 JH1, 31.63 nM for JAK1 JH1, 18.68 nM for JAK3 JH1, and 10.76 nM for TYK2 JH1, demonstrating significant selectivity for JAK2. |
|---|---|
| ln Vitro |
NVP-BSK805 (BSK 805) is a JAK2 inhibitor; its IC50 values for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1 are 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM, individually. The activity of FL JAK2 V617F and FL JAK2 wt, which have IC50 values of 0.56 ± 0.04 and 0.58 ± 0.03 nM, respectively, is inhibited by NVP-BSK805. At 0.43 ± 0.02 nM, NVP-BSK805 has an estimated ATP-competitive Ki. AML cell lines expressing JAK2V617F and having a GI50 of less than 100 nM are inhibited in their proliferation by NVP-BSK805. When applied at dosage of ≥100 nM, NVP-BSK805 inhibits STAT5 phosphorylation and, in JAK2V617F-mutant cell lines, exhibits a bias towards JAK2 inhibition over JAK1 and JAK3 inhibition. Better P-gp inhibitory action is achieved with NVP-BSK805 (5 μM). Ten micrograms of NVP-BSK805 is more effective than five micrograms in sensitizing drug-resistant KBV20C cancer cells to VIC treatment[2].
NVP-BSK805 inhibits JAK2 with an IC50 of 0.48 nM, showing >20-fold selectivity over JAK1, JAK3, and TYK2. It is a highly selective JAK2 inhibitor. In cell-based assays, NVP-BSK805 effectively blocks STAT5 phosphorylation downstream of JAK2 activation, inhibits proliferation of JAK2V617F-driven cell lines, and induces apoptosis in JAK2-dependent cells. |
| 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].
No specific in vivo efficacy data are reported. As a potent and selective JAK2 inhibitor, NVP-BSK805 is expected to demonstrate efficacy in mouse models of myeloproliferative neoplasms (e.g., JAK2V617F transgenic models), including reduction of splenomegaly, normalization of blood cell counts, and reduction of inflammatory cytokines. However, these studies have not been published. The compound remains a valuable research tool for JAK2 biology. |
| Enzyme Assay |
Cell-free JAK2 kinase activity assays are performed using recombinant human JAK2 enzyme. The enzyme is incubated with a peptide substrate and ATP in the presence of increasing concentrations of NVP-BSK805 (0.001-10,000 nM) in assay buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT). After 30-60 min at 30degC, the reaction is terminated, and IC50 is determined by measuring phosphorylated substrate via luminescence (ADP-Glo) or 33P incorporation. Selectivity is assessed using JAK1, JAK3, and TYK2 assays under similar conditions.
|
| Cell Assay |
JAK2V617F-mutant cell lines (e.g., HEL92.1.7, SET-2) or Ba/F3 cells expressing JAK2V617F are seeded in 96-well plates and treated with NVP-BSK805 at various concentrations (0.001-1000 nM) for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay. Apoptosis is measured by Annexin V/PI staining and flow cytometry. JAK2-mediated STAT5 phosphorylation at Tyr694 is measured by phospho-flow cytometry or Western blot of cell lysates. IC50 values for inhibition of cell proliferation and STAT5 phosphorylation are determined.
|
| Animal Protocol |
No specific in vivo animal protocols are published for NVP-BSK805. For potential in vivo studies, NVP-BSK805 would be formulated in a suitable vehicle (e.g., 0.5% methylcellulose, or 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline) and administered orally or intraperitoneally to mice at doses of 10-100 mg/kg. JAK2V617F transgenic mice or xenograft models with JAK2V617F-driven tumors could be used. Efficacy endpoints include tumor volume measurement, spleen weight, blood cell counts, and STAT5 phosphorylation in tissues. No such studies have been reported.
|
| ADME/Pharmacokinetics |
No specific PK data are reported for NVP-BSK805. The molecular weight is 490.55 (C27H28F2N6O) for the free base, and 563.47 for the dihydrochloride salt. CAS 1092499-93-8. The compound is typically supplied as a dihydrochloride salt. Solubility: DMSO (10-50 mg/mL). PK parameters (t1/2, Cmax, AUC, oral bioavailability) have not been characterized. As an ATP-competitive kinase inhibitor, it is expected to have moderate oral bioavailability, but this is speculative.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are reported for NVP-BSK805. As a JAK2 inhibitor, potential toxicities include cytopenias (anemia, thrombocytopenia, neutropenia) due to JAK2's role in hematopoiesis, as well as gastrointestinal effects. Standard safety assessments (hERG, Ames, repeat-dose toxicity) have not been published. No clinical trials have been conducted. The compound is not FDA-approved. For research use only.
|
| References |
|
| Additional Infomation |
Other information: NVP-BSK805 (CAS 1092499-93-8) is a research compound, not FDA-approved. It is a potent and selective ATP-competitive JAK2 inhibitor with an IC50 of 0.48 nM and >20-fold selectivity over JAK1, JAK3, and TYK2. It is valuable for studying JAK2-driven myeloproliferative neoplasms, inflammatory diseases, and JAK2 signaling pathways. Synonyms: BSK805. Purity ≥98%. For research use only.
|
| Molecular Formula |
C27H28F2N6O-HCL
|
|---|---|
| Molecular Weight |
527.01
|
| Exact Mass |
490.229
|
| CAS # |
1092499-93-8
|
| Related CAS # |
NVP-BSK805 dihydrochloride;1942919-79-0;NVP-BSK805 trihydrochloride;2320258-95-3
|
| PubChem CID |
46398810
|
| Appearance |
Off-white to yellow solid powder
|
| Density |
1.4
|
| Melting Point |
137℃
|
| LogP |
6.065
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
36
|
| Complexity |
696
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CNCCC1N2C=C(C=N2)C3=NC4=C(C=CC=C4N=C3)C5=CC(=C(C(=C5)F)CN6CCOCC6)F.Cl.Cl
|
| InChi Key |
IBPVXAOOVUAOKJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H28F2N6O/c28-23-12-18(13-24(29)22(23)17-34-8-10-36-11-9-34)21-2-1-3-25-27(21)33-26(15-31-25)19-14-32-35(16-19)20-4-6-30-7-5-20/h1-3,12-16,20,30H,4-11,17H2
|
| Chemical Name |
4-[[2,6-difluoro-4-[3-(1-piperidin-4-ylpyrazol-4-yl)quinoxalin-5-yl]phenyl]methyl]morpholine
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 125 mg/mL (254.82 mM)
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
