IKKβ-IN-5
IKKβ-IN-5 is an orally active and selective IKKβ inhibitor with an IC50 of 7.5 nM. IKKβ-IN-5 directly inhibits IKKβ phosphorylation and attenuates NF κB mediated inflammatory and survival signals while promoting autophagy flux. IKKβ-IN-5 exhibits a 6-fold selectivity forIKKβ over the homologous kinase IKKα. IKKβ-IN-5 exerts robust antiproliferative effects through a dual mechanism involving G₂/M phase cell cycle arrest and autophagy activation, even under inflammatory stimulation in vitro. IKKβ-IN-5 demonstrates favorable pharmacokinetics and suppresses tumor growth in vivo. IKKβ-IN-5 can be used for colorectal cancer and potentially other inflammation driven malignancies research.
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- 화학식: C23H24FN7
- 분자량:417.48
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
제품 설명
IC50 & Target
[1]|
IKK-β 7.5 nM (IC50) |
In Vitro
IKKβ-IN-5 (compound LP46) (0-2 μM, 48 h) exhibits robust antiproliferative activity in RKO and HCT116 cells and low toxicity in NCM460 cells[1].
IKKβ-IN-5 (0.75-3.0 μM, 48 h) impacts protein expression of IKKβ phosphorylation and its downstream target IκBα by directly inhibiting the phosphorylation of IKKβ in RKO and HCT116 cells[1].
IKKβ-IN-5 (0.75-3.0 μM, 7 days) has long-term antiproliferative effects in RKO and HCT116 cells[1].
IKKβ-IN-5 (0.75-3.0 μM, 48 h) exerts the antiproliferative effects through a dual mechanism ( including inducing G2/M phase cell cycle arrest and activating autophagy) even in the presence of inflammatory stimuli, and has ability to block NF-κB pathway activation suppressing downstream inflammatory responses in RKO and HCT116 cells[1].
IKKβ-IN-5 (3 μM, 48 h) directly counteracts IKKβ-mediated pro-inflammatory and ant autophagy effects in IKKβ knockdown CRC cells or IKKβ overexpression CRC cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT116, RKO, and NCM460 cells
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Concentration:0, 0.4 0.8, 1.2, 1.6 and 2.0 μM
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Incubation Time:48 h
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Result:Exhibited potent inhibitory activity, with IC50 values of 3.94 μM for RKO and 2.59 μM for HCT116.
Showed significantly lower toxicity in NCM460 cells, with an IC50 of 21.25 μM.
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Cell Line:RKO and HCT116 cells
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Concentration:0.75, 1.5, and 3 μM
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Incubation Time:48 h
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Result:Significantly reduced phosphorylation of both IKKβ and IκBα in a dose-dependent manner.
Induced greater inhibition of IKKβ phosphorylation.
Had no significant impact on either the expression or phosphorylation of TAK1 or MAP3K1.
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Cell Line:RKO and HCT116 cells
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Concentration:0.75, 1.5, and 3 μM
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Incubation Time:7 days
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Result:Observed Dose-dependent suppression of colony formation.
Demonstrated superior efficacy at the highest dose.
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Cell Line:RKO and HCT116 cells
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Concentration:0.75, 1.5, and 3 μM
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Incubation Time:48 h
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Result:Revealed a significant accumulation of RKO and HCT116 cells in the G2/M phase.
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Cell Line:RKO and HCT116 cells
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Concentration:0.75, 1.5, and 3 μM
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Incubation Time:48 h
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Result:Significantly inhibited DNA synthesis in both RKO and HCT116 cells.
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Cell Line:RKO and HCT116 cells
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Concentration:0.75, 1.5, and 3 μM
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Incubation Time:48 h
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Result:Dose-dependently increased expression levels of key autophagy-related markers, Beclin1 and LC3A/B both markers in RKO and HCT116 cells.
Enhanced expression of Beclin1 and LC3A/ B in these cells in RKO and HCT116 cells with TNF-α (HY-P1875).
Reduced p65 expression and inhibited its nuclear translocation in a dose-dependent manner.
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Cell Line:RKO and HCT116 cells
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Concentration:0.75, 1.5, and 3 μM
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Incubation Time:48 h
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Result:Significantly down regulated the expression of TNF-α, IL-6, and IL-1β in a dose dependent manner.
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Cell Line:IKKβ knockdown CRC cells or IKKβ overexpression CRC cells
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Concentration:3 μM
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Incubation Time:48 h
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Result:Reduced the phosphorylation levels of both IκBα and p65, while concurrently increasing the expression of key autophagy markers, Beclin1 and LC3A/B and exhibited superior efficacy in inhibiting IKKβ phosphorylation and suppressing NF-κB signaling upon TNF-α stimulation in IKKβ knockdown cells.
Increased p-IκBα and p-p65 levels and reduced Beclin1 and LC3A/B expression upon TNF-α stimulation in overexpression of IKKβ cells.
Decreased NF-κB phosphorylation and restoration of autophagy-related protein levels, even under TNF-α stimulation and IKKβ-overexpressing conditions.
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Cell Line:HCT116, RKO, and NCM460 cells
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Concentration:0, 0.4 0.8, 1.2, 1.6 and 2.0 μM
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Incubation Time:48 h
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Result:Exhibited potent inhibitory activity, with IC50 values of 3.94 μM for RKO and 2.59 μM for HCT116.
Showed significantly lower toxicity in NCM460 cells, with an IC50 of 21.25 μM.
- Western Blot
- BrdU Incorporation Assay
- Patient-Derived Orthotopic Xenograft (PDOX)
- Protocol for Cell Cycle
- Research Protocol for Inflammation-related Diseases
- Cell Viability Determination by MTT Colorimetric Assay
- Kinase activity and phosphorylation assays
- Flow cytometric DNA-content cell-cycle staining
- Autophagy
- Protocol for Pharmacokinetic Study
- Patient-Derived Xenograft (PDX)
- Protocol for Kinase activity and phosphorylation assays
- Lysosome and acidic-vesicle live-cell staining
- Subcutaneous Cell-Line-Derived Xenograft
- Macroautophagy Solutions
- Orthotopic Cell-Line Xenograft
Chemical Information
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분자량 417.48
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화학식 C23H24FN7
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SMILES
FC1=CN=C(N=C1C2=CC=C(C3=C2)C=NN3C)NC4=CC(N5CCN(CC5)C)=CC=C4
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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)