445430-58-0
445430-58-0 structure
- Name: BMS 345541
- Chemical Name: N'-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine
- CAS Number: 445430-58-0
- Molecular Formula: C14H17N5
- Molecular Weight: 255.318
- Catalog: Biochemical Inhibitor Nuclear transcription factor (NF-κB) IκB/IKK inhibitor
- Create Date: 2018-12-24 21:05:06
- Modify Date: 2024-01-18 22:00:24
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BMS-345541 free base 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.
| Name | N'-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine |
|---|---|
| Synonyms |
1,2-Ethanediamine, N-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)-
N-(1,8-Dimethylimidazo[1,2-a]quinoxalin-4-yl)-1,2-ethanediamine Kinome_3215 BMS-345541 N-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine BMS 345541 UNII-26SU0NEF5F BMS345541 BMS-345541 (free base) |
| Description | BMS-345541 free base 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. |
|---|---|
| Related Catalog | |
| Target |
IKK-2:0.3 μM (IC50) IKK-1:4 μM (IC50) |
| 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[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]. |
| 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 mM Tris-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[1]. |
| Cell Assay | SK-MEL-5 cells are treated with BMS-345541 at different concentrations (0, 1.0, 10, and 100 μM) 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[2]. |
| Animal Admin | Mice[1] 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. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 449.5±45.0 °C at 760 mmHg |
| Molecular Formula | C14H17N5 |
| Molecular Weight | 255.318 |
| Flash Point | 225.6±28.7 °C |
| Exact Mass | 255.148392 |
| PSA | 68.24000 |
| LogP | 2.08 |
| Vapour Pressure | 0.0±1.1 mmHg at 25°C |
| Index of Refraction | 1.696 |
| Storage condition | -20℃ |