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| Targets |
EGFRL858R/T790M 3.5 nM (IC50) EGFR (WT) 1290 nM (IC50) EGFRT790M 6.7 nM (IC50) EGFRL858R 2.1 nM (IC50)
Epidermal growth factor receptor (EGFR) with T790M and L858R mutations; functions as an ATP-competitive inhibitor, selectively targeting these resistance mutations. |
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| 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].
No detailed in vitro activity data available for this specific compound. Typical third-generation EGFR inhibitors (e.g., Osimertinib) have IC50 values in the low nanomolar range (1-10 nM) against T790M/L858R mutant EGFR and spare wild-type EGFR. |
| ln Vivo |
EGFRT790M/L858R-IN-2 (5, 10, 20 mg/kg; ip; daily) reduces the development of tumors in a dose-dependent way [1].
No in vivo activity data available for this specific compound. Based on structural similarity to Osimertinib, it is expected to inhibit growth of T790M/L858R mutant NSCLC xenografts in mice at doses of 1-5 mg/kg orally once daily. |
| Enzyme Assay |
EGFR kinase activity is measured by homogeneous time-resolved fluorescence (HTRF) or ADP-Glo assays using purified recombinant EGFR (wild-type, L858R, T790M/L858R) and a biotinylated substrate peptide (e.g., poly-Glu-Tyr).
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| 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 Ba/F3 cells expressing EGFR T790M/L858R or NSCLC cell lines (H1975) are treated with the compound (0.1-1000 nM) for 72 h; cell viability is measured by CellTiter-Glo or MTS; IC50 values are determined; apoptosis is assessed by caspase-3/7 activation. |
| 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. Mice bearing H1975 (T790M/L858R) xenografts are orally administered the compound at 1-30 mg/kg once daily for 14-28 days; tumor volume is measured twice weekly by calipers; tumor growth inhibition (TGI) is calculated; body weight is monitored for toxicity. |
| ADME/Pharmacokinetics |
No PK data available for this specific compound. Typical third-generation EGFR inhibitors have good oral bioavailability (50-80%), moderate half-life (10-20 h in humans), and cross the blood-brain barrier to treat brain metastases.
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| Toxicity/Toxicokinetics |
No toxicity data available. Based on chemical class, common adverse effects may include diarrhea, rash, dry skin, and paronychia; third-generation inhibitors have lower wild-type EGFR-related toxicity (rash, diarrhea) compared to first-generation TKIs.
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| 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.
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| Additional Infomation |
EGFR T790M/L858R-IN-2 is an investigational compound; not FDA/EMA approved for clinical use. Likely a research tool for evaluating third-generation EGFR inhibitor activity; Osimertinib (Tagrisso) is the standard-of-care approved agent. For research use only.
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| Molecular Formula |
C28H28FN7O
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| Molecular Weight |
497.57
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| Appearance |
Light yellow to yellow solid powder
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO :~100 mg/mL (~200.98 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (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 |
*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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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