| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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Purity: ≥98%
| Targets |
The primary target of this compound is the EGFR tyrosine kinase (ErbB1). It acts as an ATP-competitive inhibitor, binding to the ATP-binding site in the EGFR kinase domain and preventing ATP binding and receptor phosphorylation. This inhibits downstream signaling pathways involved in cell proliferation and survival. The compound is highly selective for EGFR over HER4 and 55 other kinases. Additionally, it directly depolymerizes microtubules, representing a secondary mechanism of action.
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| ln Vitro |
At lower dosages, apoptosis is successfully induced by EGFR-IN-12 (EGFR inhibitor 324674; 0-2 µM; 48 hours; HT29 and SW480 cells) therapy [2]. Treatment with EGFR-IN-12 (EGFR inhibitor 324674; 0-3 µM; 3 hours; HT29 and SW480 cells) reduced the downstream AKT signaling pathway and EGFR activation in a dose-dependent manner [2]. With an IC50 of 1.96 µM and 1.04 µM, respectively, EGFR-IN-12 (EGFR inhibitor 324674) suppresses the growth of HT29 and SW480 cells [2]. When U-2OS cells were pretreated with EGFR-IN-12 (Compound 1; 10 µM), the autophosphorylation of the wild-type receptor was totally blocked. Furthermore, EGFR-IN-12's inhibitory action is totally ineffective against the T766M mutant receptor [1].
In vitro, EGFR inhibitor shows potent enzymatic activity with an IC50 of 21 nM against EGFR kinase. It blocks receptor autophosphorylation in cellular assays, indicating functional target engagement. The compound induces apoptosis in cancer cells through inhibition of EGFR signaling, which involves downregulation of the anti-apoptotic protein survivin. Its ability to directly depolymerize microtubules adds to its antiproliferative effects, making it effective in various cancer cell lines. |
| ln Vivo |
In vivo, this EGFR inhibitor has been studied for potential therapeutic applications in non-small cell lung cancer, colorectal cancer, and pancreatic cancer. By inhibiting EGFR kinase activity and inducing microtubule depolymerization, it reduces tumor cell proliferation and increases apoptosis. The compound's antitumor activity has been demonstrated in preclinical xenograft models, where it inhibits tumor growth. Its dual mechanism may overcome resistance associated with single-target EGFR inhibitors.
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| Enzyme Assay |
In vitro enzyme assays for EGFR kinase inhibition typically use a recombinant EGFR kinase domain and a peptide substrate in the presence of ATP. The compound is incubated at various concentrations, and kinase activity is measured by quantifying phosphorylated substrate using methods such as ELISA, scintillation proximity assay, or mobility shift assays. IC50 values are calculated from dose-response curves. Selectivity profiling against a panel of kinases is performed to assess specificity.
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| Cell Assay |
Apoptosis analysis[1]
Cell Types: HT29 and SW480 Cell Tested Concentrations: 0 µM, 1 µM, 2 µM Incubation Duration: 48 hrs (hours) Experimental Results: Induction of apoptosis in HT29 cells and SW480 cells. Western Blot Analysis[1] Cell Types: HT29 and SW480 Cell Tested Concentrations: 0 µM, 0.1 µM, 0.3 µM, 1 µM, 3 µM Incubation Duration: 3 hrs (hours) Experimental Results: Inhibition of EGFR activation and downstream AKT signaling in a dose-dependent manner . For in vitro cellular assays, cancer cell lines (e.g., A431, HCC827, or H1975) expressing wild-type or mutant EGFR are cultured and treated with the compound. Receptor autophosphorylation is assessed by Western blotting using phospho-specific EGFR antibodies following compound treatment. Cell viability is measured using MTT, CCK-8, or ATP-lite assays. Apoptosis is evaluated by caspase-3/7 activity, Annexin V staining, or sub-G1 cell cycle analysis. Survivin expression is measured to confirm mechanism. |
| Animal Protocol |
In vivo animal studies typically use subcutaneous xenograft models in immunodeficient mice bearing EGFR-dependent human tumor cell lines. The compound is administered orally or intraperitoneally at various doses. Tumor volume is measured twice weekly using calipers. At study termination, tumors are excised for analysis of EGFR phosphorylation, apoptosis markers, and microtubule status. Body weight and general health are monitored to assess tolerability. Efficacy is compared to vehicle and standard-of-care EGFR inhibitors.
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| ADME/Pharmacokinetics |
As a small molecule EGFR inhibitor with molecular weight of 413.4 g/mol, this compound is expected to have good oral bioavailability and cell permeability. It is an ATP-competitive inhibitor that likely undergoes hepatic metabolism. Pharmacokinetic properties such as half-life, clearance, and volume of distribution would be determined in preclinical species. The compound's irreversible binding mechanism may result in prolonged target engagement relative to reversible inhibitors, potentially affecting dosing frequency and pharmacodynamic duration.
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| Toxicity/Toxicokinetics |
Toxicity data for this specific EGFR inhibitor is limited in publicly available sources. As a tyrosine kinase inhibitor, potential adverse effects may include skin rash, diarrhea, and hepatotoxicity, which are class effects of EGFR inhibitors. The compound's ability to depolymerize microtubules may also cause myelosuppression and peripheral neuropathy, similar to microtubule-targeting agents. Safety pharmacology studies would evaluate cardiovascular, respiratory, and CNS effects. Maximum tolerated dose is typically determined in rodent models.
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| References |
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| Additional Infomation |
Epidermal growth factor receptor tyrosine kinase inhibitors refer to any drugs that can inhibit the activity of epidermal growth factor receptor (EGFR) tyrosine kinase.
This EGFR inhibitor (CAS 879127-07-8) is a research-grade chemical probe used to investigate both the EGFR pathway and microtubule dynamics. It is a 4,6-disubstituted pyrimidine that acts as an ATP-competitive, irreversible, and highly selective EGFR inhibitor. The compound is cell-permeable and induces apoptosis with antitumor activity. It is not an approved therapeutic drug but serves as a valuable tool for cancer research, particularly for studying drug resistance mechanisms and combination therapies targeting both receptor tyrosine kinases and the cytoskeleton. |
| Molecular Formula |
C21H18F3N5O
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|---|---|
| Molecular Weight |
413.4
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| Exact Mass |
413.146
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| CAS # |
879127-07-8
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| Related CAS # |
879127-07-8
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| PubChem CID |
9549299
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
605.9±55.0 °C at 760 mmHg
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| Flash Point |
320.2±31.5 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.682
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| LogP |
5.71
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
586
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YOHYSYJDKVYCJI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H18F3N5O/c22-21(23,24)14-3-1-4-15(9-14)27-18-11-19(26-12-25-18)28-16-5-2-6-17(10-16)29-20(30)13-7-8-13/h1-6,9-13H,7-8H2,(H,29,30)(H2,25,26,27,28)
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| Chemical Name |
N-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide
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| Synonyms |
EGFR inhibitor EGFR-inhibitor EGFRinhibitor
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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 : ~250 mg/mL (~604.74 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 | 2.4190 mL | 12.0948 mL | 24.1896 mL | |
| 5 mM | 0.4838 mL | 2.4190 mL | 4.8379 mL | |
| 10 mM | 0.2419 mL | 1.2095 mL | 2.4190 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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