| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg | |||
| Other Sizes |
| Targets |
EGFR-IN-1 HCl targets the epidermal growth factor receptor (EGFR), specifically the L858R/T790M mutant form. It is an irreversible inhibitor that covalently binds to the kinase domain of the mutant EGFR. Its 100-fold selectivity for the mutant over wild-type EGFR reduces potential toxicity in normal tissues.
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| ln Vitro |
EGFR-IN-1 hydrochloride (compound 24) had a substantial antiproliferative effect on H1975 and HCC827 cells, with IC50 values of 4 and 28 nM, respectively, after being applied for 72 hours (10 μM) [1]. In H1975 and HCC827 cells, EGFR-IN-1 hydrochloride suppresses p-EGFR with IC50 values of 4 and 9 nM, respectively. A panel of 100 kinases is highly selective for EGFR-IN-1 [1].
In vitro, EGFR-IN-1 HCl is a potent inhibitor of the L858R/T790M mutant EGFR with 100-fold selectivity over wild-type EGFR. It shows potent anti-tumor and anti-proliferative activity in H1975 cells (which harbor the L858R/T790M mutation) and mutant HCC827 cells with IC50s of 4 and 28 nM, respectively. Its irreversible binding ensures sustained inhibition. |
| ln Vivo |
EGFR-IN-1 hydrochloride (30 mg/kg; oral; once daily for 2 weeks) revealed considerable tumor growth inhibition without noticeable weight loss [1]. EGFR-IN-1 hydrochloride was assessed in a time-course PD experiment at an oral dose of 30 mg/kg. EGFR-IN-1 reduces EGFR phosphorylation by >50%, lasting >12 hours. EGFR-IN-1 achieved a maximum concentration of 0.10 μM at 2 hours, with a systemic exposure (AUC0-inf.) of 0.33 μM. h[1].
In vivo, EGFR-IN-1 HCl (30 mg/kg; p.o.; daily for 2 weeks) displays significant tumor growth inhibition with no observed loss in body weight. It is evaluated in a time course pharmacodynamic experiment upon oral dosing at 30 mg/kg. The compound's oral bioavailability and efficacy make it a promising candidate for treating gefitinib-resistant NSCLC. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for EGFR-IN-1 HCl measures its ability to inhibit EGFR kinase activity. The assay is performed using purified EGFR enzymes (wild-type and L858R/T790M mutant) and a peptide substrate. The compound's ability to inhibit substrate phosphorylation is measured, and IC50 values are calculated. The 100-fold selectivity for the mutant over wild-type is confirmed in these assays.
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| Cell Assay |
Cell proliferation experiment [1]
Cell Types: NSCLC cell line H1975 (T790M/L858R), HCC827 (Δ746-750) Tested Concentrations: 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of H1975 non-small cell lung cancer cell line and the first mutant The IC50 for HCC827 cell line was 4 and 28 nM, respectively. In vitro cellular studies are conducted using NSCLC cell lines, including H1975 (L858R/T790M) and HCC827 (mutant) cells. Cells are treated with EGFR-IN-1 HCl at various concentrations. Cell viability is assessed using MTT or CellTiter-Glo assays. EGFR phosphorylation and downstream signaling (AKT, ERK) are measured by Western blot. Apoptosis is assessed by Annexin V/PI staining or caspase-3 activity assays. |
| Animal Protocol |
Animal/Disease Models: Female athymic nude mice (H1975 tumor xenograft) [1]
Doses: 30 mg/kg Route of Administration: po; one time/day for 2 weeks Experimental Results: resulted in significant tumor growth inhibition, and no body weight was observed alleviate. In vivo animal experiments are performed using xenograft models of gefitinib-resistant NSCLC. Tumor-bearing mice are administered EGFR-IN-1 HCl via oral gavage at 30 mg/kg daily for 2 weeks. Tumor volume is measured over time. Pharmacodynamic studies evaluate EGFR phosphorylation and downstream signaling in tumor tissues. Body weight is monitored to assess tolerability. |
| ADME/Pharmacokinetics |
EGFR-IN-1 HCl has a molecular formula and molecular weight consistent with its structure. It is soluble in DMSO and other organic solvents. For storage, it should be kept at -20°C, protected from light and moisture. The compound is supplied with high purity for research purposes. For in vivo administration, appropriate formulations should be used. It is an orally active compound.
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| Toxicity/Toxicokinetics |
As a potent and irreversible EGFR inhibitor, EGFR-IN-1 HCl is not intended for human use as a research chemical. Its toxicological profile is not fully characterized. Standard laboratory safety precautions should be followed when handling it. Its effects are related to its mechanism as an EGFR mutant-selective inhibitor, which could have significant biological consequences.
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| References |
[1]. Wurz RP, et al. Oxopyrido[2,3-d]pyrimidines as Covalent L858R/T790M Mutant Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors. ACS Med Chem Lett. 2015 Jul 27;6(9):987-92.
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| Additional Infomation |
EGFR-IN-1 HCl is also known as EGFR-IN-1 hydrochloride. It is an orally active and irreversible L858R/T790M mutant selective EGFR inhibitor. The compound potently inhibits gefitinib-resistant EGFR L858R, T790M with 100-fold selectivity over wild-type EGFR. It is used in research on non-small cell lung cancer (NSCLC) and drug resistance mechanisms.
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| Molecular Formula |
C28H31CLN6O4
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|---|---|
| Molecular Weight |
551.04
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| Exact Mass |
550.209
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| CAS # |
2227455-78-7
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| Related CAS # |
EGFR-IN-1 TFA;2753348-63-7
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| PubChem CID |
146026038
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| Appearance |
Typically exists as solid at room temperature
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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 |
10
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| Heavy Atom Count |
39
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| Complexity |
866
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=O)N(C2=NC(=NC=C12)NC3=C(C=C(C=C3)OCCN(C)C)OC)C4=CC=CC(=C4)NC(=O)C=C.Cl
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| InChi Key |
SDTFYMHVYLJYFV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H30N6O4.ClH/c1-6-25(35)30-19-8-7-9-20(15-19)34-26(36)14-18(2)22-17-29-28(32-27(22)34)31-23-11-10-21(16-24(23)37-5)38-13-12-33(3)4;/h6-11,14-17H,1,12-13H2,2-5H3,(H,30,35)(H,29,31,32);1H
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| Chemical Name |
N-[3-[2-[4-[2-(dimethylamino)ethoxy]-2-methoxyanilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]phenyl]prop-2-enamide;hydrochloride
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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) |
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
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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 | 1.8148 mL | 9.0738 mL | 18.1475 mL | |
| 5 mM | 0.3630 mL | 1.8148 mL | 3.6295 mL | |
| 10 mM | 0.1815 mL | 0.9074 mL | 1.8148 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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