EGFR-IN-218
EGFR-IN-218 is an orally effective EGFR inhibitor with IC50 values of 3.85, 0.40, and 140.5 nM against EGFRWT, EGFRL858R/T790M, and EGFRL858R/T790M/C797S, respectively. EGFR-IN-218 inhibits EGFR phosphorylation and downstream ERK1/2 signaling, and exhibits in vivo antitumor activity. EGFR-IN-218 can be used for research on EGFR-mutant non-small cell lung cancer, glioblastoma, and brain metastasis.
For research use only. We do not sell to patients.
- CAS No.: 2410789-80-7
- Formula: C34H39FN8O2
- Molecular Weight:610.72
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
All EGFR Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
EGFRWT 3.85 nM (IC50) |
EGFRL858R/T790M 0.4 nM (IC50) |
EGFRL858R/T790M/C797S 140.5 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A-431 | IC50 |
2.53 μM
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Antiproliferative activity against human A431 cells harboring EGFRWT assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human A431 cells harboring EGFRWT assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
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42561559 |
| H1975 | IC50 |
0.61 μM
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Antiproliferative activity against human H1975 cells expressing EGFRL858R/T790M assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human H1975 cells expressing EGFRL858R/T790M assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
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42561559 |
| U-87MG ATCC | IC50 |
8.44 μM
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Antiproliferative activity against human U87 MG cells harboring EGFRWT assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
Antiproliferative activity against human U87 MG cells harboring EGFRWT assessed as reduction in cell viability incubated for 72 hrs by MTT assay.
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42561559 |
| BaF3 | IC50 |
2.25 μM
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Antiproliferative activity against Ba/F3-EGFRL858R/T790M/C797S cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against Ba/F3-EGFRL858R/T790M/C797S cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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42561559 |
In Vitro
EGFR-IN-218 (compound 8m) (0.45-1000 nM) inhibits EGFRWT, EGFRL858R/T790M, and EGFRL858R/T790M/C797S kinase activity with IC50 values of 3.85, 0.40, and 140.5 nM, respectively[1].
EGFR-IN-218 (1 μM) shows inhibition rates of 102.23%, 99.97%, 97.29%, 90.84%, and 73.53% against HER2, EGFR, HER4, FRK, and BRK, respectively, in a 76-tyrosine kinase panel screen[1].
EGFR-IN-218 (1-100 nM; 48 h) dose-dependently decreases EGFR and ERK1/2 phosphorylation in H1975 and PC-9 cells; at 10 nM, it inhibits p-EGFR and p-ERK1/2 more potently than Osimertinib[1].
EGFR-IN-218 (0.03-100 μM; 72 h) reduces the viability of A431, H1975, U87 MG, and U87-EGFRvIII cells with IC50 values of 2.53, 0.61, 8.44, and 10.35 μM, respectively[1].
EGFR-IN-218 (72 h) reduces Ba/F3-EGFRL858R/T790M/C797S cell viability with an IC50 of 2.25 μM, superior to Osimertinib (HY-15772) at 12.03 μM[1].
EGFR-IN-218 (48 h) increases the G0/G1 phase proportion in H1975 cells from 66.46% to 84.18% and 85.19%, respectively, and decreases the S phase proportion from 27.06% to 6.24% and 6.56%, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:H1975, PC-9
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Concentration:1, 10, 100 nM
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Incubation Time:48 h
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Result:Dose-dependently decreased EGFR phosphorylation.
Decreased phospho-ERK1/2 levels.
At 10 nM, suppressed EGFR phosphorylation more strongly than Osimertinib.
At 10 nM, suppressed ERK1/2 phosphorylation more strongly than Osimertinib.
Parmacokinetics
| Species | Dose | Route | F | Cmax | Tmax | MRT0-t | MRT0-∞ | T1/2 | AUC0-t | AUC0-∞ | Vz | CL |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 4 mg/kg | i.v. | / | 481.36 μg/L | 0.46 h | 9.90 h | 12.29 h | 10.23 h | 4790.42 μg/L·h | 5058.05 μg/L·h | 40511.82 L/kg | 2313.12 L/h/kg |
| Rat[1] | 20 mg/kg | p.o. | 31.5 % | 1317.18 μg/L | 2.90 h | 6.75 h | 6.82 h | 7.94 h | 7971.30 μg/L·h | 7977.94 μg/L·h | 6865.66 L/kg | 643.00 L/h/kg |
In Vivo
EGFR-IN-218 (30 mg/kg/day; 15 days) inhibits intracranial tumor growth in intracranial H1975-Luc brain metastasis BALB/c nude mice; supplementary bioluminescence imaging on day 7 and day 15 both shows suppressed tumor burden; and it prolongs the survival of H1975-Luc brain metastasis model mice[1].
EGFR-IN-218 (5, 10 mg/kg; p.o.; once daily; 14 days) reduces EGFR phosphorylation in H1975 subcutaneous xenograft tumor tissues, with a greater degree of inhibition than 5 mg/kg Osimertinib[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (female, 5-7 weeks old)[1]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Inhibited tumor growth with TGI rates of 94.18% at 5 mg/kg and 96.10% at 10 mg/kg.
Suppressed EGFR phosphorylation relative to vehicle controls.
Chemical Information
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CAS No. 2410789-80-7
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Molecular Weight 610.72
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Formula C34H39FN8O2
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SMILES
FC(C=C1)=CC=C1C2=NC=CN2C3=CC(NC4=C(OC)C=C(N5CCC(N6CCN(C)CC6)CC5)C(NC(C=C)=O)=C4)=NC=C3
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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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
EGFR-IN-218 Related Classifications
HY-189291 Related Classifications
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