1. NF-κB Metabolic Enzyme/Protease Immunology/Inflammation Apoptosis
  2. IKK Heme Oxygenase (HO) Keap1-Nrf2 Reactive Oxygen Species (ROS) Ferroptosis
  3. JHB-17

JHB-17 is an IKKβ inhibitor with blood-brain barrier permeability, with an IC50 of 1.1 μM and a KD of 1.293 μM. JHB-17 is a non-ATP competitive inhibitor targeting the allosteric site of IKKβ, and it inhibits the phosphorylation of IKKβ. JHB-17 promotes the nuclear translocation of Nrf2, upregulates the expression of HO-1, SLC7A11 and glutathione, and reduces ROS to exert antioxidant effects. JHB-17 reduces cerebral infarction volume and improves neurobehavioral function. JHB-17 can be used in the research of cerebral ischemia-reperfusion injury.

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JHB-17

JHB-17 Chemical Structure

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Description

JHB-17 is an IKKβ inhibitor with blood-brain barrier permeability, with an IC50 of 1.1 μM and a KD of 1.293 μM. JHB-17 is a non-ATP competitive inhibitor targeting the allosteric site of IKKβ, and it inhibits the phosphorylation of IKKβ. JHB-17 promotes the nuclear translocation of Nrf2, upregulates the expression of HO-1, SLC7A11 and glutathione, and reduces ROS to exert antioxidant effects. JHB-17 reduces cerebral infarction volume and improves neurobehavioral function. JHB-17 can be used in the research of cerebral ischemia-reperfusion injury[1].

IC50 & Target[1]

IKKβ

1.1 μM (IC50)

IKK-β

1.293 μM (Kd)

HO-1

 

In Vitro

JHB-17 potently inhibits IKKβ kinase activity in a cell-free system with an IC50 of 1.1 μM, which is approximately 70 times more potent than EF24; it has a KD of 1.293 μM for binding to wild-type IKKβ, and its binding affinity to IKKβK428A and IKKβQ432A mutant proteins is reduced[1].
JHB-17 (0.625-5 μM; 1 h or 18 h) increases the survival rate of H2O2-damaged SH-SY5Y cells in a concentration-dependent manner[1].
JHB-17 (5 μM; 1 h or 18 h) significantly reduces lipid peroxidation levels (MDA levels) and ROS accumulation in SH-SY5Y cells damaged by H2O2 after 1 h or 18 h of pretreatment[1].
JHB-17 (5 μM; 6 h) promotes Nrf2 nuclear translocation[1].
JHB-17 (1.25-5 μM; 18 h) upregulates the expression of HO-1 protein in SH-SY5Y cells in a dose-dependent manner[1].
JHB-17 (5 μM; 18 h pretreatment, 6 h H2O2 exposure) inhibits H2O2-induced phosphorylation of IKKβ and upregulates the expression of HO-1 protein in SH-SY5Y cells after 18 h of pretreatment followed by 6 h of H2O2 exposure[1].
JHB-17 (5 μM; 18 h pretreatment, followed by 24 h H2O2 exposure) loses its cytoprotective effect against H2O2-induced damage in SH-SY5Y cells when IKKβ is overexpressed, which confirms that IKKβ is its key target[1].
JHB-17 acts in a dose-dependent manner, and this effect occurs after 18 h of pretreatment followed by 2 h of exposure to H2O2[1].
JHB-17 (1.25-5 μM; 18 h pretreatment, 24 h H2O2 exposure) upregulates the expression of SLC7A11, increases intracellular GSH levels and reduces lipid ROS, and inhibits H2O2-induced ferroptosis in SH-SY5Y cells in a dose-dependent manner[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: SH-SY5Y human neuroblastoma cells (H2O2-induced oxidative damage model)
Concentration: 0.625, 1.25, 2.5, 5 μM
Incubation Time: 1 h or 18 h (pretreatment); 24 h (H2O2 exposure)
Result: Protected SH-SY5Y cells from H2O2-induced damage in a concentration-dependent manner for both 1 h and 18 h pretreatments, with significant protective activity observed at concentrations as low as 0.625 μM.

Immunofluorescence[1]

Cell Line: SH-SY5Y cells
Concentration: 5 μM
Incubation Time: 6 h
Result: Significantly enhanced Nrf2 fluorescence signal within the nuclei of SH-SY5Y cells, indicating increased Nrf2 nuclear translocation.

Western Blot Analysis[1]

Cell Line: SH-SY5Y cells
Concentration: 1.25, 2.5, 5 μM
Incubation Time: 18 h
Result: Dose-dependently increased HO-1 protein levels in SH-SY5Y cells after 18 h incubation.
At 5 μM, induced stronger HO-1 expression than JHA-7 and TBHQ.
Upregulated the expression of SLC7A11.

Western Blot Analysis[1]

Cell Line: SH-SY5Y cells (H2O2-induced oxidative damage model)
Concentration: 5 μM
Incubation Time: 18 h (pretreatment); 6 h (H2O2 exposure)
Result: Significantly inhibited H2O2-induced IKKβ phosphorylation and upregulated HO-1 protein expression in SH-SY5Y cells.

Cell Viability Assay[1]

Cell Line: IKKβ-overexpressing SH-SY5Y cells exposed to H2O2
Concentration: 5 μM; 1200 ng/mL IKKβ plasmid
Incubation Time: 18 h (pretreatment); 24 h (H2O2 exposure); 6 h (transfection)
Result: Significantly increased cell viability after H2O2 damage in cells with normal IKKβ expression.
Almost completely abolished this protective effect in IKKβ-overexpressing cells.
Parmacokinetics
Species Dose Route T1/2 Tmax Cmax AUC0-t AUC0-∞ MRT0-t MRT0-∞ F
Mice[1] 15 mg/kg i.p. 7.57 h 0.25 h 56.3 ng/mL 192.0 ng·h/mL 205.0 ng·h/mL 4.99 h 7.19 h 22.1 %
In Vivo

JHB-17 (15 mg/kg; i.p.; administered 2 h before modeling) significantly reduces cerebral infarct volume and improves neurological function in rat MCAO/R model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

432.34

Formula

C23H23Cl2NO3

SMILES

O=C1/C(CC/C1=C\C2=CC=C(O)C(O)=C2)=C/C3=CC=C(N(CCCl)CCCl)C=C3

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
References
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Product Name:
JHB-17
Cat. No.:
HY-184115
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