EGFR-IN-181
EGFR-IN-181 is an orally active, potent, brain-penetrant EGFRL858R/T790M/C797S triple mutations inhibitor (IC50 = 1.32 nM). EGFR-IN-181 can inhibit EGFR phosphorylation (p-EGFR) and phosphorylation of its downstream signaling proteins AKT (p-AKT) and ERK (p-ERK). EGFR-IN-181 can induce apoptosis and cause G2 phase arrest. EGFR-IN-181 can be used for the study of non-small cell lung cancer (NSCLC) and brain metastases.
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- 화학식: C24H28ClN6OP
- 분자량:482.95
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
제품 설명
IC50 & Target
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Akt |
EGFR (C797S/T790M/L858R) |
In Vitro
EGFR-IN-181 (Compound D18) (0.001-1000 μg/mL, 48 h) shows significant anti-proliferative activity against various EGFR mutant cell lines and has a high IC50 against normal cells (MCR-5, HEK293, LX-2)[1].
EGFR-IN-181 (50-500 nM, 24 h) concentration-dependently inhibits EGFR phosphorylation (p-EGFR) and its downstream signaling proteins AKT (p-AKT) and ERK (p-ERK) in NCI-H1975 cells (carrying EGFRL858R/T790M/C797S)[1].
EGFR-IN-181 (50-500 nM, 24 h) concentration-dependently induces apoptosis in NCI-H1975 EGFRL858R/T790M/C797S cells and causes G2 phase arrest[1].
EGFR-IN-181 inhibits hERG potassium channels in HEK293 cells with an IC50 of 10.55 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A549 cell line: harboring EGFRWT BaF3™ cell line: engineered BaF3 cell line, harboring EGFRL858R/T790M/C797S NCI–H1975 cell line: harboring EGFRL858R/T790M/C797S PC-9 cell line: harboring EGFRDel19 H1975 cell line: harboring EGFRL858R/T790M MCR-5, HEK293, LX-2
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Concentration:0.001 μg/mL, 0.01 μg/mL, 0.1 μg/mL, 1 μg/mL, 10 μg/mL, 100 μg/mL, 1000 μg/mL
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Incubation Time:48 h
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Result:A549 (IC50 = 2.63 μM)
PC-9 (IC50 = 0.012 μM)
H1975 (IC50 = 0.027 μM)
BaF3TM (IC50 = 0.049 μM)
NCI–H1975 (IC50 = 0.87 μM)
MCR-5 (IC50 = 4.51 μM)
HEK293 (IC50 = 36.17 μM)
LX-2 (IC50 = 4.84 μM)
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Cell Line:NCI-H1975 EGFRL858R/T790M/C797S
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Concentration:50 nM, 100 nM, 500 nM
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Incubation Time:24 h
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Result:Concentration-dependently inhibited EGFR phosphorylation (p-EGFR) and its downstream signaling proteins AKT (p-AKT) and ERK (p-ERK) in NCI-H1975 cells EGFRL858R/T790M/C797S; at a concentration of 500 nM, EGFR phosphorylation was completely inhibited.
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Cell Line:NCI-H1975 EGFRL858R/T790M/C797S cells
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Concentration:50 nM, 150 nM, 250 nM, 500 nM
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Incubation Time:24 h
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Result:Induced apoptosis in a degree-dependent manner, achieving an apoptosis rate of 37.94% at a concentration of 500 nM.
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Cell Line:NCI-H1975 EGFRL858R/T790M/C797S cells
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Concentration:50 nM, 150 nM, 250 nM, 500 nM
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Incubation Time:24 h
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Result:Induced G2 phase arrest in a concentration-dependent manner, with the proportion of cells in G2 phase being 22.57 % at 50 nM and increasing to 65.98 % at 500 nM.
Parmacokinetics
| Species | Dose | Route | Cmax | AUC0-∞ | MRT0-∞ | Tmax | T1/2 | CL | F |
|---|---|---|---|---|---|---|---|---|---|
| Rat | 5 mg/kg | i.v. | 806.67 ng/mL | 660.39 ng·h/mL | 0.95 h | 0.08 h | 1.05 h | 7610.97 mL/h/kg | / |
| Rat | 50 mg/kg | p.o. | 516.67 ng/mL | 1700.94 ng·h/mL | 4.07 h | 0.28 h | 3.15 h | 34089.95 mL/h/kg | 25.76 % |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:A xenograft tumor model was established using female BALB/c nude mice (6-8 weeks old) by subcutaneous transplantation of NCI-H1975 cells EGFRL858R/T790M/C797S triple mutations)[1].
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Dosage:12.5 mg/kg, 25 mg/kg
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Administration:P.o., once daily for 15 days
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Result:At a dose of 12.5 mg/kg, the tumor growth inhibition rate (TGI) was 53.64 %; at a dose of 25 mg/kg, the TGI was 91.04 %.
The average tumor weight was significantly lower than that of the control group.
Did not experience a significant decrease in body weight, and H&E staining of the major organs (heart, liver, spleen, lung, and kidney) showed no lesions or organ failure.
Chemical Information
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분자량 482.95
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화학식 C24H28ClN6OP
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SMILES
CP(C)(C1=CC=CC=C1NC2=NC(NC3=CC4=C(N(CCN(C)C)C=C4)C=C3)=NC=C2Cl)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
EGFR-IN-181 Related Classifications
HY-178939 Related Classifications
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