| Description | IMD-0354 is an IKKβ inhibitor and blocks IκBα phosphorylation in NF-κB pathway. | ||||||||||||||||
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| In vitro | IMD-0354 (< 5="" μm)="" inhibits="" the="" expression="" of="" nf-κb="" as="" well="" as="" the="" translocation="" of="" nf-κb="" to="" the="" nucleus="" in="" hmc-1="" cells.="" imd-0354="" suppresses="" cell="" proliferation="" in="" a="" time-="" and="" dose-dependent="" manner="" in="" hmc-1="" cells.="" imd-0354="" (0.5="" μm)="" almost="" inhibits="" the="" proliferation="" of="">G559 cells and IC-2V814 cells. IMD-0354 (0.5 μM) results in arrest of the cell cycle at the G0/G1 phase in HMC-1 cells. IMD-0354 (1 μM) increases the number of cells with hypodiploid DNA content in HMC-1 cells. IMD-0354 (<1 μm)="" decreases="" the="" ratio="" of="" cells="" in="" s="" and="" g2/m="" phases="" in="" hmc-1="" cells.="" imd-0354="" (1="" μm)="" downregulates="" cyclin="" d3="" expression="" as="" well="" as="" prb="" phosphorylation="" level="" in="" a="" time-dependent="" manner="" in="" hmc-1="" cells.="" imd-0354="">< 10="" μm)="" has="" no="" influence="" on="" the="" signals="" of="" stat3="" and="" stat6,="" whereas="" the="" phosphorylation="" of="" stat1="" and="" stat5="" is="" very="" slightly="" suppressed="" at="" high="" concentrations="" in="" hmc-1="" cells.="" imd-0354="" suppresses="" the="" translocation="" of="" nf-κb="" to="" the="" nucleus="" in="" cbhcmcs="" after="" 24="" hours="" in="" a="" dose-dependent="" manner.="">[1] IMD-0354 inhibits 98.5% of NF-κB activity at a concentration of 10 μg/ml in HepG2 cells. [2] IMD-0354 (1 μM) ameliorates the TNFα-induced decrease in the adiponectin concentration in the media, when the TNFα (6 nM) and insulin (100 nM) are administered simultaneously in 3T3-L1 adipocytes serum-starved for 12 h. IMD-0354 (1 μM) restores the phosphorylation of Akt down-regulated by the TNFα treatment, when the TNFα (6 nM) and insulin (100 nM) are administered simultaneously in 3T3-L1 adipocytes serum-starved for 12 h. [3] IMD-0354 (1 μM) inhibits phosphorylation of IκBα and nuclear translocation of nuclear factor-kappa B (NF-κB) induced by tumor necrosis factor-α (TNF-α) in cultured cardiomyocytes. IMD-0354 (1 μM) significantly reduces TNF-α-induced production of interleukin-1β and monocyte chemoattractant protein-1 from cultured cardiomyocytes. [4] | ||||||||||||||||
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| In vivo | IMD-0354 at 5 mg/kg also significantly decreases NF-κB, but the magnitude of the decrease is lower than with 20 mg/kg IMD-0354 in lungs of OVA-sensitized mice. IMD-0354 (20 mg/kg) ameliorates airway hyperresponsiveness and reduces the numbers of bronchial eosinophils and mucus-producing cells in OVA-sensitized mice. IMD-0354 (20 mg/kg) also reduces the total numbers of cells and eosinophils in bronchoalveolar lavage fluid in OVA-sensitized mice. IMD-0354 (20 mg/kg) inhibits the production of Th2 cytokines such as interleukin (IL)-5 and IL-13 and eotaxin in the airways and/or lungs of OVA-sensitized mice, but it does not affect the restoration of Th1 cytokines such as IL-12 and interferon-gamma under the same experimental conditions. IMD-0354 (20 mg/kg) results in a partial decrease in serum IgE concentration in OVA-sensitized mice. [2] IMD-0354 significantly decreases the plasma glucose levels in KKAy mice treated with and fed an HF diet in an dose-dependent manner without influence of body weight. [3] IMD-0354 (10 mg/kg) results in a significant dose-dependent reduction of the infarction area/area at risk ratio and the preservation of fractional shortening ratio. [4] |
