EGFR-IN-173
EGFR-IN-173 is an orally active, pan-mutant EGFR tyrosine kinase inhibitor that targets EGFR 19del, L858R/T790M and C797S triple-mutations, potently inhibiting EGFR19del/T790M/C797S with an IC50 of 1.19 nM while showing over 100-fold selectivity for mutant over wild-type EGFR (IC50 = 19.362 μM against WT). EGFR-IN-173 significantly inhibits cell migration, induces apoptosis in non-small cell lung cancer (NSCLC) cells. EGFR-IN-173 inhibits EGFR phosphorylation and suppresses the downstream pathways (MAPK/ERK, AKT, STAT3). EGFR-IN-173 exhibits antitumor efficacy in NSCLC and Ba/F3 xenograft models. EGFR-IN-173 can be used for NSCLC research.
For research use only. We do not sell to patients.
- Formula: C28H36ClN8O2P
- Molecular Weight:583.06
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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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All EGFR Isoforms
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Biological Activity
EGFR-IN-173 (compound D10) (0.001-0 μM, 72 h) displays broad and robust antiproliferative activity various EGFR mutants, with IC50 values of 0.69 nM in HCC827 cells (EGFR19del), 0.242 μM in H1975 cells (EGFRL858R/T790M), 0.192 μM in Ba/F3-EGFR19del/T790M/C797S cells, and 1.303 μM in Ba/F3-EGFRL858R/T790M/C797S, and shows more than 100-fold selectivity for mutant over WT EGFR (IC50 = 19.362 μM against WT) [1].
EGFR-IN-173 occupies the active site of EGFR and forms important hydrogen bonds with Lys728 and Ser797[1].
EGFR-IN-173 (10-100 nM, 14 days) dose-dependently inhibits colony formation in the NSCLC HCC827 cells, suppressing their long-term proliferative capacity[1].
EGFR-IN-173 (10-100 nM, 0-48 h) effectively suppresses the migration of NSCLC H1975 cells in a concentration-dependent manner[1].
EGFR-IN-173 (20-200 nM, 48 h) induces G0/G1 phase arrest in a dose-dependent manner in HCC827 cells[1].
EGFR-IN-173 (1-2000 nM, 48 h) induces both early and late-stage apoptosis in a concentration-dependent manner by triggering hallmark morphological events, including chromatin condensation, nuclear fragmentation, and the formation of apoptotic bodies[1].
EGFR-IN-173 (0.01-1 μM, 48 h) inhibits EGFR phosphorylation and suppresses the downstream pathways (MAPK/ERK, AKT, STAT3) in a dose-dependent manner, ultimately triggering apoptosis and the degradation of signaling proteins like ERK1/2[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCC827 cells and H1975-OR cells
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Concentration:0.01, 0.1 and 1 μM
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Incubation Time:48 h
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Result:Exhibited superior dose-responsive inhibition of EGFR autophosphorylation at Tyr1068, a key molecular switch for downstream pathway activation.
Suppressed ERK1/2 phosphorylation (T202/Y204, T185/Y187) at 0.1 μM with 35.6 % inhibition, demonstrating potent blockade of the MAPK signaling axis.
Almost completely abrogated EGFR activation at 1 μM, whereas BLU-945 (HY-144680) showed weak inhibition at an equivalent concentration in HCC827 cells.
Significantly reduced ERK1/2 protein level at 100 nM.
Reduced p-Stat3 (Tyr705), p-Akt (Ser473), and p-Mek1/2 (Ser217/221) levels.
Increased cleaved caspase-3 at 100 nM, suggesting that the concurrent downregulation of ERK1/2 resulted from apoptosis-induced protein degradation.
Suppressed EGFR phosphorylation in H1975-OR cells at 100 nM.
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Cell Line:H1975 cells
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Concentration:10 and 100 nM
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Incubation Time:0, 24 and 48 h
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Result:Significantly decreased wound closure compared to the negative control, indicating a dose-dependent inhibition of cell migration.
Resulted in a significantly larger wound area than the control over time.
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Cell Line:HCC827 cells
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Concentration:20 and 200 nM
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Incubation Time:48 h
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Result:Dose-dependently accumulated cells in the G0/G1 phase, increasing the population from 74.40% at 20 nM to 94.58% at 200 nM.
Induced G0/G1 phase cell cycle arrest (94.58 %) comparable to Osimertinib (HY-15772) (94.92 %) at 200 nM.
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Cell Line:HCC827 and H1975 cells
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Concentration:20, 200, and 2000 nM (H1975 cells, DAPI Staining); 20, 200, and 2000 nM (HCC827 cells, AO/EB Staining); 1, 10, and 100 nM (HCC827 cells, Hoechst 33342/PI Staining); 10, 100, and 1000 nM (HCC827 cells, Flow Cytometry)
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Incubation Time:48 h
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Result:Induced dose-dependent nuclear condensation and fragmentation, with more pronounced effects than Osimertinib at equivalent concentrations.
Triggered nuclear condensation in HCC827 cells at 20 nM.
Induced a progressive rise in late-stage apoptosis in a concentration-dependent manner.
Exhibited concentration-dependent chromatin condensation and subsequent nuclear fragmentation, both hallmarks of apoptosis.
Induced the formation of apoptotic bodies.
Resulted in 6.36 %, 19.9 % and 31.6 % early apoptosis at 10, 100 and 1000 nM.
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Cell Line:HCC827 cells
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Concentration:10, 50 and 100 nM
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Incubation Time:14 days
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Result:Dose-dependently suppressed colony formation, exhibiting 32.8 % inhibition at 10 nM compared to the control.
Showed 58.3 % inhibition at 50 nM and nearly complete suppression at 100 nM.
EGFR-IN-173 (50 mg/kg, P.O., daily for 17 days) exhibits a certain inhibitory effect on the EGFR19del/T790M/C797S triple mutation in Ba/F3-EGFR19del/T790M/C797S xenograft mouse model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c nude mice, (6-8 weeks) subcutaneously injected with Ba/F3-EGFR19del/ T790M/C797S cells[1]
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Dosage:50 mg/kg
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Administration:P.O., daily for 17 days
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Result:Significantly reduced tumor volume and weight compared to the vehicle control group.
Reduced tumor cell density and increased intertumoral fibrosis.
Exhibited no significant body weight loss during the dosing period.
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Animal Model:Male BALB/c nude mice (6-8 weeks) subcutaneously injected with HCC827 cells[1]
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Dosage:25 and 50 mg/kg
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Administration:P.O., daily for 12 days
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Result:Significantly suppressed tumor growth and reduced excised tumor weight at both low and high doses, demonstrating its potent efficacy and favorable dose tolerance.
Exhibited no significant body weight loss or clinically observable adverse effects at the dose of 50 mg/kg, supporting a favorable safety profile with minimal systemic toxicity.
Chemical Information
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Molecular Weight 583.06
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Formula C28H36ClN8O2P
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SMILES
CP(C)(C1=CC=CC=C1NC2=NC(NC3=CC(C4=CN(C)N=C4)=C(N(CCN(C)C)C)C=C3OC)=NC=C2Cl)=O
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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-173 Related Classifications
HY-175864 Related Classifications
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