Physicochemical Properties
| Molecular Formula | C28H28FN7O |
| Molecular Weight | 497.57 |
| Appearance | Light yellow to yellow solid powder |
| 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 | EGFRL858R/T790M 3.5 nM (IC50) EGFR (WT) 1290 nM (IC50) EGFRT790M 6.7 nM (IC50) EGFRL858R 2.1 nM (IC50) |
| ln Vitro | In H1975 and HCC827 cells, EGFRT790M/L858R-IN-2 (compound 28f) (0.1, 1, 10 µM; 4 h) dose-dependently decreases the expression of p-EGFR, P-AKT, and P-ERK1/2 [1]. In H1975 and HCC827 cells, EGFRT790M/L858R-IN-2 (0.1, 1, 10 µM; 48 hours) promotes apoptosis and cell cycle arrest in the G1 phase [1]. In a dose-dependent way, EGFRT790M/L858R-IN-2 (0.1, 1, 10 µM; 14 days) suppresses the formation of colonies and cell migration [1]. |
| ln Vivo | EGFRT790M/L858R-IN-2 (5, 10, 20 mg/kg; ip; daily) reduces the development of tumors in a dose-dependent way [1]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: H1975, HCC827, A549, A431cells Tested Concentrations: 0.1, 1, 10 µM Incubation Duration: 4 h Experimental Results: diminished the expression of p-EGFR, P-AKT, P-ERK1/2 in a dose-dependent manner in H1975, HCC827 cells, demonstrated a weak inhibitory effect on EGF-induced EGFR and AKT and ERK1/2 phosphorylation in A549 and A431 cells. Apoptosis Analysis[1] Cell Types: H1975, HCC827, A549, A431cells Tested Concentrations: 0.1, 1, 10 µM Incubation Duration: 48 h Experimental Results: Dramatically induced apoptosis of H1975 and HCC827 cells in a dose-dependent manner, demonstrated weaker apoptosis-inducing ability than osimertinib in A549 and A431 cells, inducing only 14.80 and 17.93% apoptosis, respectively, at 10 μM. Cell Cycle Analysis[1] Cell Types: H1975, HCC827, A549, A431cells Tested Concentrations: 0.1, 1, 10 μM Incubation Duration: 48 h Experimental Results: Induced cell cycle arrest in the G1 phase with the G0/G1 Phase ratios are approximately 80.5% for H1975 and approximately 81.1% for HCC827, approximately 63.8% for A549 and appr |
| Animal Protocol |
Animal/Disease Models: 6-8 weeks, BALB/c female nude mice(H1975 cell xenografts)[1] Doses: 5, 10, 20 mg/kg Route of Administration: Ip; once per day Experimental Results: Inhibited tumor growth, both in volume and weight in a dose-dependent manner. |
| References | [1]. Pei J, et al. Design, Synthesis, and Antitumor Activity of Potent and Selective EGFR L858R/T790M Inhibitors and Identification of a Combination Therapy to Overcome Acquired Resistance in Models of Non-small-cell Lung Cancer. J Med Chem. 2023 Apr 27;66(8):5719-5752. |
Solubility Data
| Solubility (In Vitro) | DMSO :~100 mg/mL (~200.98 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 | 2.0098 mL | 10.0488 mL | 20.0977 mL | |
| 5 mM | 0.4020 mL | 2.0098 mL | 4.0195 mL | |
| 10 mM | 0.2010 mL | 1.0049 mL | 2.0098 mL |