EGFR-IN-1
EGFR-IN-1 (compound 24) is an orally active and irreversible L858R/T790M mutant selective EGFR inhibitor. EGFR-IN-1 potently inhibits Gefitinib-resistant EGFR L858R, T790M with 100-fold selectivity over wild-type EGFR. EGFR-IN-1 displays strong antiproliferative activity against the H1975 cells and the first line mutant HCC827 cells. Antitumor activity.
For research use only. We do not sell to patients.
- CAS No.: 1625677-63-5
- Formula: C28H30N6O4
- Molecular Weight:514.58
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All EGFR Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
EGFRL858R/T790M |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A-431 | IC50 |
1054 nM
Compound: 24
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Inhibition of wild type EGFR phosphorylation in human A431 cells after 60 mins by mesoscale multiplex assay
Inhibition of wild type EGFR phosphorylation in human A431 cells after 60 mins by mesoscale multiplex assay
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[PMID: 26396685] |
| A-431 | IC50 |
2400 nM
Compound: 24
|
Cytotoxicity against human A431 cells expressing wild-type EGFR assessed as inhibition of cell proliferation after 72 hrs by CellTiter-Glo assay
Cytotoxicity against human A431 cells expressing wild-type EGFR assessed as inhibition of cell proliferation after 72 hrs by CellTiter-Glo assay
|
[PMID: 26396685] |
| HCC827 | IC50 |
28 nM
Compound: 24
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Cytotoxicity against human HCC827 cells harboring EGFR 746 to 750 deletion mutant assessed as inhibition of cell proliferation after 72 hrs by CellTiter-Glo assay
Cytotoxicity against human HCC827 cells harboring EGFR 746 to 750 deletion mutant assessed as inhibition of cell proliferation after 72 hrs by CellTiter-Glo assay
|
[PMID: 26396685] |
| NCI-H1975 | IC50 |
4 nM
Compound: 24
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Cytotoxicity against human NCI-H1975 cells harboring EGFR L858R/T790M double mutant assessed as inhibition of cell proliferation after 72 hrs by CellTiter-Glo assay
Cytotoxicity against human NCI-H1975 cells harboring EGFR L858R/T790M double mutant assessed as inhibition of cell proliferation after 72 hrs by CellTiter-Glo assay
|
[PMID: 26396685] |
| NCI-H1975 | IC50 |
4 nM
Compound: 24
|
Inhibition of EGFR L858R/T790M double mutant phosphorylation in human NCI-H1975 cells after 60 mins by mesoscale multiplex assay
Inhibition of EGFR L858R/T790M double mutant phosphorylation in human NCI-H1975 cells after 60 mins by mesoscale multiplex assay
|
[PMID: 26396685] |
In Vitro
EGFR-IN-1 (10 μM; 72 hours) displays strong antiproliferative activity against the H1975 and HCC827 cells with IC50s of 4 and 28 nM, respectively[1].
EGFR-IN-1 inhibits p-EGFR in H1975 and HCC827 cells with IC50s of 4 and 9 nM, respectively. EGFR-IN-1 highly selective against a panel of 100 kinases[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:NSCLC cell lines H1975 (T790M/L858R), HCC827 (∆746-750)
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Concentration:10 μM
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Incubation Time:72 hours
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Result:Inhibited H1975 nonsmall cell lung cancer cell line and the first line mutant HCC827 cell line with IC50s of 4 and 28 nM, respectively.
In Vivo
EGFR-IN-1 evaluates in a time course PD experiment upon oral dosing at 30 mg/kg. EGFR-IN-1 shows a >50% inhibition of phosphorylation of EGFR for >12 h. EGFR-IN-1 reaches maximal concentration of 0.10 μM at 2 h and systemic exposure (AUC0-inf.) is 0.33 μM. h[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female athymic nude mice (H1975 Tumor Xenograft)[1]
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Dosage:30 mg/kg
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Administration:p.o.; daily for 2 weeks
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Result:Led to significant tumor growth inhibition with no observed loss in body weight.
Chemical Information
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CAS No. 1625677-63-5
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Molecular Weight 514.58
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Formula C28H30N6O4
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SMILES
COC(C=C(OCCN(C)C)C=C1)=C1NC2=NC=C3C(N(C4=CC=CC(NC(C=C)=O)=C4)C(C=C3C)=O)=N2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)