NVP-BSK805 is an ATP-competitive JAK2 inhibitor (antagonist) with IC50s of 0.48 nM, 31.63 nM, 18.68 nM and 10.76 nM for JAK2 JH1 (JAK homolog 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively.

Physicochemical Properties

Molecular Formula	C27H28F2N6O
Molecular Weight	490.55
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
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)

Biological Activity

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)
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].
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].
References	[1]. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010 Jul;9(7):1945-55. [2]. 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.

Solubility Data

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0385 mL	10.1926 mL	20.3853 mL
	5 mM	0.4077 mL	2.0385 mL	4.0771 mL
	10 mM	0.2039 mL	1.0193 mL	2.0385 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.