BMS-554417
BMS-554417 is an orally active inhibitor of insulin receptor and insulin-like growth factor-I receptor (IGF-1R) kinases, with IC50 values of 50.6 nM and 67.9 nM, respectively. BMS-554417 blocks downstream signal transduction via the ERK and PI3K/Akt pathways. BMS-554417 induces G0-G1 cell cycle arrest, prevents cyclin D1 accumulation in the nucleus, triggers mitochondrial pathway-mediated apoptosis, promotes HER2 phosphorylation, and inhibits the proliferation and growth of cancer cells. BMS-554417 can be used in research related to colon cancer, ovarian cancer, and breast cancer.
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- No. CAS: 468741-42-6
- Fòrmula: C28H30ClN7O2
- Peso molecular:532.05
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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
|
insulin receptor 50.6 nM (IC50) |
IGF-1R 67.9 nM (IC50) |
ERK |
PI3K |
Akt |
HER2 |
In Vitro
BMS-554417 (5-20 μM; 1 h) inhibits basal and ligand-induced IGF-IR phosphorylation in MCF-7 and OV202 cells, and insulin-induced insulin receptor phosphorylation in MCF-7 cells, without altering total receptor protein levels[1].
BMS-554417 (5-20 μM; 1 h) inhibits ligand-induced and basal ERK1/2 and Akt (Ser473) phosphorylation in MCF-7 and OV202 cells, without affecting total ERK1/2, Akt, p38, or JNK protein levels[1].
BMS-554417, a dual IGF-IR/IR tyrosine kinase inhibitor with balanced potency against both receptors, inhibits the growth of human colon (Colo205), ovarian (OV202), and MCF-7 breast cancer cells in vitro[2].
BMS-554417 completely inhibits IGF-1R/InsR phosphorylation and increases HER2 phosphorylation (with further enhancement by EGF) in OV202 ovarian cancer cells[3].
BMS-554417 (72 h) exhibits synergistic antiproliferative activity with the panHER inhibitor BMS-599626 (HY-10251) in OV202 ovarian cancer cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7 human breast cancer cells, OV202 human epithelial ovarian cancer cells
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Concentration:5 μM (MCF-7), 20 μM (OV202)
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Incubation Time:1 h
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Result:Completely inhibited LR3 IGF-I-induced IGF-IR phosphorylation in MCF-7 cells to nonstimulated levels.
Completely inhibited insulin-induced insulin receptor phosphorylation in MCF-7 cells to nonstimulated levels.
Greatly reduced basal and LR3 IGF-I-stimulated IGF-IR phosphorylation in OV202 cells.
Left total IGF-IR and insulin receptor protein levels unchanged across all treatment groups.\nInhibited LR3 IGF-I-induced phosphorylation of ERK1/2 and Akt (Ser473) in MCF-7 cells to basal levels.
Inhibited insulin-induced phosphorylation of ERK1/2 and Akt (Ser473) in MCF-7 cells to basal levels.
Inhibited basal and LR3 IGF-I-stimulated phosphorylation of ERK1/2 in OV202 cells.
Inhibited basal and LR3 IGF-I-stimulated phosphorylation of Akt (Ser473) in OV202 cells.
Left total ERK1/2, Akt, p38, and JNK protein levels unchanged across all treatment groups.
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Cell Line:MCF-7 human breast cancer cells
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Concentration:5 μM
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Incubation Time:24 h
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Result:Reduced the percentage of MCF-7 cells in S phase from 45.1% (LR3 IGF-I stimulated) to 6.5%.
Dramatically reduced cyclin D1 staining intensity and nuclear localization induced by LR3 IGF-I stimulation.
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Cell Line:MCF-7 human breast cancer cells, OV202 human epithelial ovarian cancer cells, Jurkat human T-cell leukemia cells (including variants JB-6, I2.1, 5B4, 5B2)
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Concentration:IC90 concentrations (MCF-7, OV202); 2.5-10 μM (Jurkat); 10 μM (Jurkat pathway analysis)
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Incubation Time:72 h
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Result:Induced PARP-1 cleavage and nuclear fragmentation in MCF-7 and OV202 cells.
Induced dose-dependent apoptosis in Jurkat cells, with ~37% apoptotic cells at 10 μM.
Showed unaltered apoptotic response in Jurkat cells treated with death receptor pathway inhibitors (DR5:Fc, IETD(OMe)-fmk, Nok-1) or FADD-deficient I2.1 cells.
Showed markedly diminished apoptotic response in Jurkat variants overexpressing Bcl-2 (JB-6 cells) or Bcl-xL (5B4 cells).
In Vivo
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:200 mg/kg
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Administration:p.o.; twice daily; 14 days
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Result:Extended time to reach target tumor volume from 19.3 days to 35.5 days.
Reduced mean tumor volume significantly compared to vehicle controls between days 17 and 28 post-implantation.
Achieved a mean serum concentration of 30.0 μM at 6 hours after administration.
- Western Blot
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Protocol for Cell Cycle
- Breast Cancer Modeling
- Cell Viability Determination by MTT Colorimetric Assay
- Kinase activity and phosphorylation assays
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Research Protocol for Endocrine Diseases
- Apoptosis Solutions
- Protocol for Kinase activity and phosphorylation assays
Chemical Information
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No. CAS 468741-42-6
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Peso molecular 532.05
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Fòrmula C28H30ClN7O2
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SMILES
N(C[C@@H](O)C1=CC(Cl)=CC=C1)C2=C(C=3NC=4C(N3)=CC(=CC4C)N5CCN(CCC#N)CC5)C(=O)NC=C2
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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)
BMS-554417 Related Classifications
HY-10263 Related Classifications
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Keywords
- BMS-554417
- 468741-42-6
- BMS554417
- BMS 554417
- Insulin Receptor
- IGF-1R
- ERK
- PI3K
- Akt
- EGFR
- Apoptosis
- mitochondrial pathway apoptosis
- IGF1R-Sal tumor xenograft
- insulin receptor
- extracellular signal-related kinase
- insulin-like growth factor-I receptor
- cyclin D1
- carcinoma cells
- G0-G1 cell cycle arrest
- phosphoinositide 3-kinase/Akt pathways
- colon cancer
- Inhibitor
- inhibitor
- inhibit