Physicochemical Properties
| Molecular Formula | C29H31F3N8O |
| CAS # | 2904690-41-9 |
| Appearance | Typically exists as solid at room temperature |
| 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 | TrkA 3.3 nM (IC50) TrkB 6.4 nM (IC50) TrkC 4.3 nM (IC50) TRKAG667C 9.4 nM (IC50) FLT3 1.3 nM (IC50) RET 9.9 nM (IC50) VEGFR2 71.1 nM (IC50) |
| ln Vitro | At 1 μM, TRK II-IN-1 (compound 12d) exhibits nearly 70% inhibition against Kit, CSF1R, DDR1, and DDR2, and over 90% kinase inhibition against VEGFR2, RET, and FLT3[1]. Ba/F3-CD74-TRKA, Ba/F3-ETV6-TRKB, and Ba/F3-ETV6-TRKC cells are inhibited by TRK II-IN-1 (72 h), with IC50s of 26.1, 44.7, and 15.7 nM, respectively[1]. A panel of Ba/F3 cells that have been stably transformed with wild type, xDFG, and solvent-front (SF) mutant TRK fusion proteins has its proliferation suppressed by TRK II-IN-1 (72 h), with IC50s ranging from 2.6 to 143.3 nM[1]. Apoptosis is induced in Ba/F3-CD74-TRKA and Ba/F3-CD74-TRKAG667C cells by TRK II -IN-1 (0.4-500 nM; 48 h)[1]. In Ba/F3-CD74-TRKA and Ba/F3-CD74-TRKAG667C cells, TRK II-IN-1 (0.4-500 nM; 24 h) stops cell cycle progression in the G0/G1 phase[1]. The phosphorylation of TRKA, TRKAG667C kinases, and their downstream AKT, ERK, and PLCγ1 is suppressed in a dose-dependent manner by TRK II-IN-1 (0.8-500 nM; 6 h)[1]. |
| Cell Assay |
Apoptosis Analysis[1] Cell Types: Ba/ F3 stable cell lines expressing wild type and G667C mutant fusions Tested Tested Concentrations: 0.4, 2 , 10, 50 nM for Ba/F3-CD74-TRKA cells; 4, 20, 100, 500 nM for Ba/F3-CD74-TRKAG667C cells Incubation Duration: 48 hrs (hours) Experimental Results: Notable apoptotic cells (18.74% in 100 nM and 35.65 % in 500 nM) were observed in Ba/F3-CD74-TRKA cells. Induced Ba/F3-CD74-TRKAG667C cell apoptosis with 11.22% and 56.25% at the concentration of 10 nM and 50 nM, respectively. Cell Cycle Analysis[1] Cell Types: Ba/ F3 stable cell lines expressing wild type and G667C mutant fusions Tested Tested Concentrations: 0.4, 2, 10, 50 nM for Ba/F3-CD74-TRKA cells; 4, 20, 100, 500 nM for Ba/F3- CD74-TRKAG667C cells Incubation Duration: 24 hrs (hours) Experimental Results: Arrested cell cycle progression in the G0/G1 phase. Western Blot Analysis[1] Cell Types: Ba/ F3 stable cell lines expressing wild type and G667C mutant fusions Tested Tested Concentrations: 0.8, 4, 20, 100, 500 nM Incubation Duration: 6 hrs (hours) Experimental Results: Inhibited the activation of TRKA and downst |
| References |
[1]. Switch type I to type II TRK inhibitors for combating clinical resistance induced by xDFG mutation for cancer therapy. Eur J Med Chem. 2023 Jan 5;245(Pt 1):114899. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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.) |