DFX117
DFX117 is an orally active PI3Kα/c-Met inhibitor. DFX117 blocks PI3K/Akt and Met downstream signaling through selective inhibition of PI3Kα (IC50 = 0.5 nM) and c-Met tyrosine kinase activity (IC50 = 17.1 nM), and induces G0/G1 phase arrest, caspase-dependent intrinsic apoptosis (apoptosis), and PTEN upregulation in non-small cell lung cancer cells, thereby inhibiting tumor growth. DFX117 can be used for research on non-small cell lung cancer.
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- No. CAS: 2125500-60-7
- Fòrmula: C26H26F2N6O5S
- Peso molecular:572.58
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
PI3Kα 0.5 nM (IC50) |
c-Met 17.1 nM (IC50) |
Akt |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| NCI-H1975 | IC50 |
0.02 μM
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Antiproliferative activity against human lung cancer NCI-H1975 cells assessed as cell growth inhibition by SRB assay.
Antiproliferative activity against human lung cancer NCI-H1975 cells assessed as cell growth inhibition by SRB assay.
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31060329 |
| A549 | IC50 |
0.04 μM
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Antiproliferative activity against human lung cancer A549 cells assessed as cell growth inhibition by SRB assay.
Antiproliferative activity against human lung cancer A549 cells assessed as cell growth inhibition by SRB assay.
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31060329 |
| NCI-H1993 | IC50 |
0.05 μM
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Antiproliferative activity against human lung cancer NCI-H1993 cells assessed as cell growth inhibition by SRB assay.
Antiproliferative activity against human lung cancer NCI-H1993 cells assessed as cell growth inhibition by SRB assay.
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31060329 |
| HCC827 | IC50 |
0.08 μM
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Antiproliferative activity against human lung cancer HCC827 cells assessed as cell growth inhibition by SRB assay.
Antiproliferative activity against human lung cancer HCC827 cells assessed as cell growth inhibition by SRB assay.
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31060329 |
| MRC5 | IC50 |
2.89 μM
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Cytotoxicity against normal human fetal lung fibroblast MRC-5 cells assessed as cell growth inhibition by SRB assay.
Cytotoxicity against normal human fetal lung fibroblast MRC-5 cells assessed as cell growth inhibition by SRB assay.
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31060329 |
In Vitro
DFX117 inhibits the proliferation of NCI-H1975, A549, NCI-H1993, and HCC827 cells, with IC50 values of 0.02-0.08 µM[1].
DFX117 (72 h) inhibits colony formation in cultured cells[1].
DFX117 (0.1-0.4 µM; 24 h) inhibits PI3K/Akt/mTOR signaling in A549 and NCI-H1975 cells[1].
DFX117 (0.2 µM; 8 h) reduces p-Akt immunofluorescence in A549 and NCI-H1975 cells[1].
DFX117 reduces PIK3CA mRNA in A549 and NCI-H1975 cells in a concentration-dependent manner[1].
DFX117 (0.2 µM; 8 h) inhibits phosphorylated Met in A549 cells in a phosphorylated RTK array[1].
DFX117 (24 h) inhibits c-Met phosphorylation and its downstream p-RAC1, p-STAT3, and p-ERK1/2 in A549 and NCI-H1975 cells[1].
DFX117 (0.4 µM; 48 h) induces apoptosis in A549 and NCI-H1975 cells, and 0.4 µM increases Annexin V-positive cells to 26.84% and 32.75%, respectively[1].
DFX117 (0.4 µM; 48 h) activates caspase-dependent apoptosis in A549 and NCI-H1975 cells[1].
DFX117 induces apoptosis in NSCLC cells by simultaneously inhibiting c-Met and PI3Kα[2].
DFX117 (0.1-0.4 µM; 24 h) modulates cell cycle regulators and promotes G0/G1 phase arrest in A549 and NCI-H1975 cells[1].
DFX117 (24 h) induces G0/G1 cell cycle arrest in A549 and NCI-H1975 cells[1].
DFX117 is a selective PI3Kα inhibitor with an IC50 value of 0.5 nM[1].
DFX117 inhibits c-Met kinase activity with an IC50 value of 17.1 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A549 and NCI-H1975 cells
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Concentration:0.1, 0.2, 0.4 µM
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Incubation Time:24 h
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Result:Suppressed p-Akt, p-mTOR, p-p70S6K, p-GSK3β, p-4EBP1, and p-eIF4E and enhanced PTEN expression in both A549 and NCI-H1975 cells.\nIncreased p-cyclin D1 and decreased cyclin D1; suppressed c-Myc, CDK2, CDK4, cyclin E, cyclin A, Rb, and p-Rb; and upregulated p27 and p21 in A549 and NCI-H1975 cells in a concentration-dependent manner.
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Cell Line:A549 and NCI-H1975 cells
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Concentration:0.2 µM
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Incubation Time:8 h
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Result:Suppressed p-Akt expression in A549 and NCI-H1975 cells.
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Cell Line:A549 and NCI-H1975 cells
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Concentration:0.4 µM
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Incubation Time:48 h
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Result:The population of Annexin V-positive apoptotic cells increased in a concentration-dependent manner.
In A549 cells, apoptosis increased from 6.09% to 26.84% at 0.4 µM; in NCI-H1975 cells, apoptosis increased from 4.15% to 32.75% at 0.4 µM.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUCall | MRTINF_obs |
|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | p.o. | 2.1 h | 0.3 h | 4504.3 ng/mL | 3340.6 ng/mL·h | 2.2 h |
In Vivo
DFX117 (10-20 mg/kg; oral gavage; daily; 23 days) dose-dependently inhibits the growth of NCI-H1975 xenograft tumors, with a tumor volume inhibition rate of up to 81.89% at 20 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:nude mice[1]
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Dosage:5 mg/kg, 10 mg/kg, and 20 mg/kg
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Administration:p.o. (oral gavage); daily; for 23 days
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Result:Tumor volume inhibition relative to vehicle control was 48.1% at 5 mg/kg, 67.3% at 10 mg/kg, and 79.9% at 20 mg/kg.
PIK3CA mRNA levels were dose-dependently decreased in tumors.
Immunohistochemical analysis showed suppression of p-Met and p-Akt, increased cleaved caspase-3, and suppressed Ki67.
Tumor protein levels of p-Met, Grb2, p-GSK3β, p-mTOR, p-STAT3, and p-ERK1/2 were downregulated.
Changes in expression levels of apoptosis-related proteins in tumor tissues were consistent with in vitro cell culture findings, including p53, Bax, cleaved caspase-9, caspase-3, PARP, and Bcl-2.
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Animal Model:nude mice[1]
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Dosage:10 mg/kg and 20 mg/kg
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Administration:p.o. (oral gavage); daily; for 23 days
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Result:Tumor volume inhibition relative to vehicle control was 52.0% at 10 mg/kg and 81.89% at 20 mg/kg.
Tumor protein levels of p-Met, Grb2, p-GSK3β, p-mTOR, p-STAT3, and p-ERK1/2 were downregulated.
p-PI3K p85, p-Akt (Ser473), and p-Akt (Thr308) were also downregulated.
- Kinase activity and phosphorylation assays
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- Patient-Derived Xenograft (PDX)
- Apoptosis Solutions
- Patient-Derived Orthotopic Xenograft (PDOX)
- Protocol for Cell Cycle
- Protocol for Kinase activity and phosphorylation assays
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
Chemical Information
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No. CAS 2125500-60-7
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Peso molecular 572.58
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Fòrmula C26H26F2N6O5S
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SMILES
O=C(C1=CN=C2C=CC(C3=CC(NS(=O)(C4=CC=C(C=C4F)F)=O)=C(OC)N=C3)=CN21)NCCN5CCOCC5
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DFX117 Related Classifications
HY-164384 Related Classifications
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