JAK2-IN-7 is a JAK2 selectivity with IC50s of 3, 11.7 and 41 nM for cellular JAK2, SET-2 and Ba/F3V617F. The selectivity of JAK2-IN-7 is more than 14 times that of JAK1, JAK3, and FLT3. JAK2-IN-7 stimulates the cell cycle in the G0/G1 tumor phase and causes apoptosis (apoptosis). anticancer effect.

Physicochemical Properties

Molecular Formula	C26H33N7O
Molecular Weight	459.59
Exact Mass	459.274
CAS #	2593402-36-7
PubChem CID	155925850
Appearance	Off-white to light yellow solid powder
LogP	2.7
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	7
Heavy Atom Count	34
Complexity	699
Defined Atom Stereocenter Count	0
SMILES	C(N1CCC2=CC(NC3=NC=C(C)C(C4C=NN(C(C)C)C=4)=N3)=CC=C2C1)(=O)/C=C/CN(C)C
InChi Key	SURRDPSGERGIIM-VOTSOKGWSA-N
InChi Code	InChI=1S/C26H33N7O/c1-18(2)33-17-22(15-28-33)25-19(3)14-27-26(30-25)29-23-9-8-21-16-32(12-10-20(21)13-23)24(34)7-6-11-31(4)5/h6-9,13-15,17-18H,10-12,16H2,1-5H3,(H,27,29,30)/b7-6+
Chemical Name	(E)-4-(dimethylamino)-1-[6-[[5-methyl-4-(1-propan-2-ylpyrazol-4-yl)pyrimidin-2-yl]amino]-3,4-dihydro-1H-isoquinolin-2-yl]but-2-en-1-one
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

ln Vitro	In SET-2 and Ba/F3-JAK2V617F cells, JAK2-IN-7 (Compound 13ac) (0-1000 nM; 2 hours) inhibits JAK2 and STAT5 phosphorylation in a dose-dependent manner [1]. In the G0/G1 phase, JAK2-IN-7 (10-160 nM; 24 hours) causes cell arrest [1]. JAK2-IN-7 (0.05-1.6 μM; 2 hours) causes SET-2 cells to undergo apoptosis [1].
ln Vivo	JAK2-IN-7 (15-60 mg/kg; oral; given daily for 16 days) showed substantial anti-tumor effectiveness in vivo, suppressing 82.3% of tumor development in a SET-2 xenograft model [1]. JAK2-IN-7 (30-60 mg/kg; oral; once daily for 16 days) dramatically alleviated illness symptoms in the Ba/F3-JAK2V617F allograft model, normalizing spleen weights by 77.1% more than Ruxolitinib More effective. 1].
Cell Assay	Cell cycle analysis[1] Cell Types: SET-2 Cell Tested Concentrations: 10-160 nM Incubation Duration: 24 hrs (hours) Experimental Results: Cell arrest in G0/G1 phase was induced in a concentration-dependent manner. Apoptosis analysis [1] Cell Types: SET-2 Cell Tested Concentrations: 0.05-1.6 μM Incubation Duration: 2 hrs (hours) Experimental Results: Induced apoptosis of SET-2 cells.
Animal Protocol	Animal/Disease Models: Xenograft NOD/SCID mouse model inoculated with SET-2 cells [1] Doses: 15, 30 and 60 mg/kg Route of Administration: Oral daily for 16 days Experimental Results: Demonstrated significant tumor growth inhibition The effect reached 82.3%, with no obvious weight change.
References	[1]. N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms [published online ahead of print, 2020 Nov 30]. J Med Chem. 2020;10.1021/acs.jmedchem.0c01488.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~543.96 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.53 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 20.8 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: ≥ 2.08 mg/mL (4.53 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 20.8 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1759 mL	10.8793 mL	21.7585 mL
	5 mM	0.4352 mL	2.1759 mL	4.3517 mL
	10 mM	0.2176 mL	1.0879 mL	2.1759 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.