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.
IC50&Target
IKK-2
0.3 μM (IC50)
IKK-1
4 μM (IC50)
体外研究
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.
体内研究
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.
分子式
C14H17N5
分子量
255.32
CAS号
445430-58-0
运输条件
Room temperature in continental US; may vary elsewhere.