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BMS-345541

CAS No. : 445430-58-0

產(chǎn)品活性：BMS-345541 is a selective inhibitor of the catalytic subunits of IKK (IKK-2 IC₅₀=0.3 μM, IKK-1 IC₅₀=4 μM). BMS-345541 binds at an allosteric site of IKK.

研究領(lǐng)域：NF-κB

作用靶點(diǎn)：IKK

In Vitro: BMS-345541 selectively inhibits the stimulated phosphorylation of IκBα in cells (IC₅₀=4 μM). Consistent with the role of IKK/NF-κB in the regulation of cytokine transcription, BMS-345541 inhibits lipopolysaccharide-stimulated tumor necrosis factor α, interleukin-1β, interleukin-8, and interleukin-6 in THP-1 cells with IC₅₀ values in the 1 to 5 μM range. BMS-345541 treatment results in a concentration-dependent inhibition of melanoma cell proliferation in SK-MEL-5, A375, and Hs 294T cells. BMS-345541 (0, 100 μM) shows apoptotic features as revealed by TUNEL staining and nuclear condensation.

In Vivo: BMS-345541 (10 mg/kg, p.o.) results in prolonged serum drug levels, with concentrations sustained at or above 1 μM for many hours in mice. BMS-345541 dose-dependently inhibits the production of TNFα measured in the serum of animals challenged with an intraperitoneal administration of LPS. BMS-345541 (0, 10, 25, and 75 mg/kg, p.o.) effectively inhibits SK-MEL-5 tumor growth in a dose-dependent manner in the mice. Tumor-bearing mice treated with 75 mg/kg of BMS-345541 show effective inhibition of growth of SK-MEL-5, A375, and Hs 294T tumors by 86±2.8%, 69±11% and 67±3.4%, respectively.

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