PI3Kα-IN-33
PI3Kα-IN-33 is an orally active and selective PI3Kα inhibitor with an IC50 of 9.9 nM. PI3Kα-IN-33 blocks the PI3K/Akt/mTOR signaling pathway. PI3Kα-IN-33 induces apoptosis and triggers G2/M-phase arrest via Cyclin B1 and CDK1 downregulation. PI3Kα-IN-33 can be used for the research of colorectal cancer.
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- Fòrmula: C20H19N5O3
- Peso molecular:377.40
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Almacenamiento:
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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Actividad biológica
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
PI3Kα 9.9 nM (IC50) |
CDK1/cyclinB1 |
In Vitro
PI3Kα-IN-33 (Compound 8b) forms a stable, high-affinity complex with PI3Kα[1].
PI3Kα-IN-33 (48 h) potently inhibits proliferation of multiple cancer cell lines, with the highest activity against HCT-116 colorectal cancer cells (IC50 = 0.53 μM), and has reduced cytotoxicity toward normal HEK293 cells (IC50 = 7.42 μM)[1].
PI3Kα-IN-33 (2.0 μM; 12 h) effectively inhibits the migratory ability of HCT-116 colorectal cancer cells[1].
PI3Kα-IN-33 (0.5-2.0 μM; 2 weeks) inhibits colony formation of HCT-116 colorectal cancer cells in a concentration-dependent manner[1].
PI3Kα-IN-33 (0.5-2.0 μM; 48 h) induces selective G2/M-phase arrest in HCT-116 colorectal cancer cells at concentrations of 0.5, 1.0, and 2.0 μM[1].
PI3Kα-IN-33 (0.5-2.0 μM; 48 h) at concentrations of 0.5, 1.0, and 2.0 μM causes concentration-dependent downregulation of Cyclin B1 and CDK1 in HCT-116 colorectal cancer cells[1].
PI3Kα-IN-33(0.5-2.0 μM; 48 h) at concentrations of 0.5, 1.0, and 2.0 μM triggers concentration-dependent activation of the mitochondrial apoptotic pathway and induction of DNA double-strand breaks in HCT-116 colorectal cancer cells[1].
PI3Kα-IN-33 (0.5-2.0 μM; 24 h) triggers concentration-dependent mitochondrial membrane potential depolarization in HCT-116 colorectal cancer cells[1].
PI3Kα-IN-33 (0.5-2.0 μM; 48 h) induces concentration-dependent apoptosis in HCT-116 colorectal cancer cells, with 33.3% total apoptosis at 2.0 μM[1].
PI3Kα-IN-33 (1.0-5.0 μM; 48 h) concentration-dependently inhibits the PI3K/Akt/mTOR signaling pathway in HCT-116 colorectal cancer cells[1].
PI3Kα-IN-33 blocks the PI3K-Akt-mTOR axis in HCT-116 colorectal cancer cells, driving transcriptional reprogramming of oncogenic and metabolic pathways including suppressed glycolysis and MTORC1 signaling[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT-116 colorectal cancer cells
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Concentration:2.0 μM
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Incubation Time:12 h
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Result:Significantly reduced HCT-116 cell migration compared to the control, with a migration inhibition rate of approximately 75%.
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Cell Line:HCT-116 colorectal cancer cells
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Concentration:0.5 μM; 1 μM; 2.0 μM
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Incubation Time:2 weeks
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Result:Inhibited HCT-116 colony formation in a concentration-dependent manner.
At 2.0 μM, the number of surviving colonies was reduced to approximately 1 × 103, showing a strong inhibitory effect.
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Cell Line:HCT-116 colorectal cancer cells
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Concentration:0.5 μM; 1 μM; 2.0 μM
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Incubation Time:48 h
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Result:Selectively induced G2/M-phase arrest in HCT-116 cells, increasing the G2/M population from 14.2% (control) to 23.4% at 0.5 μM, while G0/G1 and S-phase fractions remained largely unchanged.
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Cell Line:HCT-116 colorectal cancer cells
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Concentration:0.5 μM; 1 μM; 2.0 μM
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Incubation Time:48 h
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Result:Induced concentration-dependent downregulation of Cyclin B1 and CDK1 protein levels, supporting blockade of the G2/M transition.\nInduced concentration-dependent increases in the Bax/Bcl-2 ratio, upregulation of cleaved caspase-9 and cleaved caspase-3, and increased levels of γ-H2AX (a marker of DNA double-strand breaks).
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Cell Line:HCT-116 colorectal cancer cells
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Concentration:0.5 μM; 1 μM; 2.0 μM
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Incubation Time:48 h
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Result:Induced apoptosis in a concentration-dependent manner, with total apoptotic cell percentages increasing to 21.66% (0.5 μM), 29.6% (1.0 μM), and 33.3% (2.0 μM).
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Cell Line:HCT-116 colorectal cancer cells
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Concentration:1 μM; 2 μM; 5 μM
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Incubation Time:48 h
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Result:Inhibited phosphorylation of PI3K, Akt, p70S6K, and 4EBP1 in a concentration-dependent manner.
At 2.0 μM, it exhibited strong inhibitory effects on p-PI3K, p-p70S6K, and p-Akt phosphorylation.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (SD) rats (male and female)[1]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:i.v. or i.g.; single dose
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Result:Exhibited an AUC0-t of 23078 μg/L·h, an AUC0-∞ of 23119 μg/L·h, a MRT0-t of 2.41 h, a MRT0-∞ of 2.45 h, a t1/2 of 2.95 h, a CL of 0.22 L/h·kg, a Vd of 0.94 L/kg, and a Cmax of 13600.39 μg/L at 5 mg/kg i.v.
Exhibited an AUC0-t of 16453 μg/L·h, an AUC0-∞ of 16481 μg/L·h, a MRT0-t of 5.89 h, a MRT0-∞ of 5.92 h, a t1/2 of 2.31 h, a CL of 0.61 L/h·kg, a Vd of 2.04 L/kg, a Cmax of 2666.62 μg/L, a tmax of 1 h, and a F of 35.6% at 10 mg/kg i.g.
Chemical Information
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Peso molecular 377.40
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Fòrmula C20H19N5O3
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SMILES
NC1=NC2=CC(C3=CC=C(N=CC(N4CCOCC4CO)=N5)C5=C3)=CC=C2O1
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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)
PI3Kα-IN-33 Related Classifications
HY-183787 Related Classifications
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