For research use only. Not for therapeutic Use.
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.
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[1]. 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[2].
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[1]. 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[2].
| Catalog Number | I003577 |
| CAS Number | 445430-58-0 |
| Synonyms | N’-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine |
| Molecular Formula | C14H17N5 |
| Purity | ≥95% |
| InChI | InChI=1S/C14H17N5/c1-9-3-4-11-12(7-9)19-10(2)8-17-14(19)13(18-11)16-6-5-15/h3-4,7-8H,5-6,15H2,1-2H3,(H,16,18) |
| InChIKey | PSPFQEBFYXJZEV-UHFFFAOYSA-N |
| SMILES | CC1=CC2=C(C=C1)N=C(C3=NC=C(N23)C)NCCN |
| Reference | [1]. Burke JR, et al. BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. J Biol Chem, 2003, 278(3), 1450-1456. [2]. Yang J, et al. BMS-345541 targets inhibitor of kappaB kinase and induces apoptosis in melanoma: involvement of nuclear factor kappaB and mitochondria pathways. Clin Cancer Res, 2006, 12(3 Pt 1), 950-960. [3]. MacMaster JF, et al. An inhibitor of IkappaB kinase, BMS-345541, blocks endothelial cell adhesion molecule expression and reduces the severity of dextran sulfate sodium-induced colitis in mice. Inflamm Res, 2003, 52(12), 508-511. |
