MCE products for research use only. We do not sell to patients.

BMS-345541 hydrochloride

MCE China：BMS-345541 hydrochloride

Brand：MedChemExpress (MCE)

Cat. No.HY-10518

CAS：547757-23-3

Purity：99.90%

Storage：4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Shipping：Room temperature in continental US; may vary elsewhere.

Description：BMS-345541 hydrochloride 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.

In Vitro：BMS-345541 inhibits IKK-2 and IKK-1 in dose-dependent manner. BMS-345541 fails to inhibit a panel of both serine/threonine and tyrosine kinases at concentrations as high as 100 μM. MS-345541 at concentrations as high as 100 μM fails to block both the anisomycin-stimulated phosphorylation of c-Jun and LPS-stimulated activation of MAPKAP K2 in THP-1 cells, as well as the EGF-stimulated phosphorylation of STAT3 in H292 cells[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].

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[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]. BMS-345541 (30 and 100 mg/kg, p.o.) is effective in blocking both clinical and histological endpoints of inflammation and injury in mice[3].

Animal Administration：BMS-345541 is administered either by intravenous tail vein injection or by peroral gavage to groups of three 18-22-g female BALB/c mice. BMS-345541 is formulated as a 2 mg/mL solution in 3% Tween 80, water. Mice receive either a 2 mg/kg (1 mL/kg) intravenous bolus or a 10 mg/kg (5 mL/kg) peroral gavage. Whole blood samples are taken from individual mice by orbital bleed and cardiac puncture at 0, 0.05, 0.25, 0.5, 1.0, 3.0, 6.0, and 8.0 h after dosing. Whole blood is centrifuged at 20×103×g for 5 min. Serum is stored at −20°C until analysis.

Cell Assay：Briefly, SK-MEL-5 cells are treated with BMS-345541 at different concentrations or for different time periods. The cells are collected by trypsinization, fixed in 70% ethanol for 2 hours on ice and stained with PI solution (PBS containing 2 μg/mL PI, 0.1% Triton X-100, and 125 units/mL RNase A) at 37°C for 30 minutes. Cell fluorescence is measured by flow cytometry with 488 nm excitation and 620 nm emission filters and resulting data are analyzed using the software program MultiCycle.

Kinase Assay：Assays measuring the enzyme-catalyzed phosphorylation of GST-IκBα are performed by adding enzyme (IKK-2, IKK-1, or IKK-ε, typically to a final concentration of 0.5 μg/mL) at 30°C to solutions of 100 μg/mL GST-IκBα and 5 μM [33P]ATP in 40 mMTris·HCl, pH 7.5, containing 4 mM MgCl2, 34 mM sodium phosphate, 3 mM NaCl, 0.6 mM potassium phosphate, 1 mM KCl, 1 mM dithiothreitol, 3% (w/v) glycerol, and 250 μg/mL bovine serum albumin. The specific activity of [33P]ATP used in the assay is 100 Ci/mmol. After 5 min, the kinase reactions are stopped by the addition of 2× LaemmLi sample buffer and heat-treated at 90°C for 1 min. The samples are then loaded on to NuPAGE 10% BisTris gels. After completion of SDS-PAGE, gels are dried on a slab gel dryer. The bands are then detected using a 445Si PhosphorImager, and the radioactivity is quantified using ImageQuant software. Under these conditions, the degree of phosphorylation of GST-IκBα is linear with time and concentration of enzyme.

IC50 & Target：IKK-2 0.3 μM (IC50) IKK-1 4 μM (IC50)

Hot selling product：8-Gingerol  | Sulfamethoxazole  | Siponimod  | RS 09  | Sodium zirconium cyclosilicate  | Motixafortide  | (±)-N-3-Benzylnirvanol  | Phosphorylcholine  | SPDB  | Limonin

Trending products：Recombinant Proteins  |  Bioactive Screening Libraries  |  Natural Products  |  Fluorescent Dye  |  PROTAC  |  Isotope-Labeled Compounds  |  Oligonucleotides

References：

[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.  [Content Brief]

[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.  [Content Brief]

[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.  [Content Brief]