JAK2/FLT3-IN-1 is an orally bioactive dual JAK2/FLT3 conjugate with IC50s of 0.7 nM, 4 nM, 26 nM and 39 nM for JAK2, FLT3, JAK1 and JAK3, respectively. JAK2/FLT3-IN- 1 has anti-cancer activity.

Physicochemical Properties

Molecular Formula	C25H34FN7O
Molecular Weight	467.582
Exact Mass	467.28
CAS #	2387765-27-5
Related CAS #	JAK2/FLT3-IN-1 TFA;2928093-29-0
PubChem CID	139600335
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	660.2±65.0 °C at 760 mmHg
Flash Point	353.1±34.3 °C
Vapour Pressure	0.0±2.1 mmHg at 25°C
Index of Refraction	1.633
LogP	3.45
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	8
Heavy Atom Count	34
Complexity	620
Defined Atom Stereocenter Count	0
InChi Key	CVLXNRIQVFIVGY-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H34FN7O/c1-17(2)33-16-19(15-28-33)24-18(3)14-27-25(30-24)29-20-5-6-23(22(26)13-20)32-9-7-21(8-10-32)31(4)11-12-34/h5-6,13-17,21,34H,7-12H2,1-4H3,(H,27,29,30)
Chemical Name	2-[[1-[2-fluoro-4-[[5-methyl-4-(1-propan-2-ylpyrazol-4-yl)pyrimidin-2-yl]amino]phenyl]piperidin-4-yl]-methylamino]ethanol
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	JAK2/FLT3-IN-1 dose-dependently downregulates p-FLT3 (0.008-1 μM; for 2 hours)[1]. JAK2/FLT3-IN-1 (5-100 nM; for 2 hours) induces apoptosis in MV4-11 cells in a dose-dependent manner [1]. With a G1/G0 percentage of 85% at 100 nM, JAK2/FLT3-IN-1 (5-100 nM; for 2 hours) significantly induces cell cycle arrest in MV4-11 cells [1].
ln Vivo	JAK2/FLT3-IN-1 (30 and 60 mg/kg/day; orally; for 14 days) displays substantial anti-tumor effects [1].
Cell Assay	Western Blot Analysis[1] Cell Types: MV4-11 and SET-2 Cell Tested Concentrations: 0.008, 0.04, 0.2, 1 μM Incubation Duration: 2 hrs (hours) Experimental Results: p-FLT3 was downregulated from 0.008 to 1μM in a dose-dependent manner. Apoptosis analysis [1] Cell Types: MV4-11 Cell Tested Concentrations: 5, 10, 50, 100 nM Incubation Duration: 2 hrs (hours) Experimental Results: It has a dose-dependent effect on inducing apoptosis of MV4-11 cells. Cell cycle analysis[1] Cell Types: MV4-11 Cell Tested Concentrations: 5, 10, 50, 100 nM Incubation Duration: 2 hrs (hours) Experimental Results: Induced cell cycle arrest at 100 nM with a G1/G0 percentage of 85%.
Animal Protocol	Animal/Disease Models: NOD/SCID mouse model [1] Doses: 30 and 60 mg/kg Route of Administration: oral; daily; 14-day Experimental Results: demonstrated significant anti-tumor effect. In the MV4-11-carrying mouse model, the tumor growth inhibition rates (TGI) were 58% and 93%, respectively.
References	[1]. Discovery of Potent and Orally Effective Dual JAK2/FLT3 Inhibitors for the Treatment of AcuteMyelogenous Leukemia and Myeloproliferative Neoplasms. J Med Chem. 2019 Oct 31.

Solubility Data

Solubility (In Vitro)

DMSO : ~35 mg/mL (~74.85 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.08 mg/mL (4.45 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 (4.45 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1387 mL	10.6934 mL	21.3867 mL
	5 mM	0.4277 mL	2.1387 mL	4.2773 mL
	10 mM	0.2139 mL	1.0693 mL	2.1387 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.