Physicochemical Properties
| Molecular Formula | C27H35F4N7O3 |
| Molecular Weight | 581.605519533157 |
| Exact Mass | 581.273 |
| CAS # | 2928093-29-0 |
| Related CAS # | JAK2/FLT3-IN-1;2387765-27-5 |
| PubChem CID | 162640797 |
| Appearance | Yellow to orange solid powder |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 13 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 41 |
| Complexity | 704 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | WIIIAEPAIQXSFK-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C25H34FN7O.C2HF3O2/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;3-2(4,5)1(6)7/h5-6,13-17,21,34H,7-12H2,1-4H3,(H,27,29,30);(H,6,7) |
| 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;2,2,2-trifluoroacetic acid |
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | JAK1 26 nM (IC50) JAK2 0.7 nM (IC50) JAK3 39 nM (IC50) FLT3 4 nM (IC50) |
| ln Vitro | JAK2/FLT3-IN-1 (0.008-1 μM; for 2 hours) (TFA) dose-dependently downregulates p-FLT3[1]. The induction of apoptosis in the MV4-11 cells is influenced in a dose-dependent manner by JAK2/FLT3-IN-1 (5-100 nM; for 2 hours) (TFA)[1]. With a G1/G0 percentage of 85% at 100 nM, JAK2/FLT3-IN-1 (5-100 nM; for 2 hours) (TFA) significantly triggers cellular cycle arrest in MV4-11 cells[1]. |
| ln Vivo | JAK2/FLT3-IN-1 (TFA) has notable anticancer effects at doses of 30 and 60 mg/kg/day; po; for 14 days[1]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: MV4-11 and SET-2 cells Tested Concentrations: 0.008, 0.04, 0.2, 1 μM Incubation Duration: For 2 hrs (hours) Experimental Results: Down-regulated p-FLT3 in a dose-dependent manner from 0.008 to 1 μM. Apoptosis Analysis[1] Cell Types: MV4-11 cells Tested Concentrations: 5, 10, 50, 100 nM Incubation Duration: For 2 hrs (hours) Experimental Results: Had a dose-dependent effect on the induction of apoptosis in the MV4- 11 cells. Cell Cycle Analysis[1] Cell Types: MV4-11 cells Tested Concentrations: 5, 10, 50, 100 nM Incubation Duration: For 2 hrs (hours) Experimental Results: Induced cell cycle arrest with a G1/G0 percentage of 85% at 100 nM. |
| Animal Protocol |
Animal/Disease Models: NOD/SCID mouse models[1] Doses: 30 and 60 mg/kg Route of Administration: Oral administration; daily; for 14 days Experimental Results: demonstrated significant antitumor effects. The tumor growth inhibitory rates (TGI) were respective 58% and 93% in the MV4-11-bearing mice model. |
| 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) | H2O : 33.33 mg/mL (57.31 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 | 1.7194 mL | 8.5968 mL | 17.1937 mL | |
| 5 mM | 0.3439 mL | 1.7194 mL | 3.4387 mL | |
| 10 mM | 0.1719 mL | 0.8597 mL | 1.7194 mL |