547757-23-3

Usage

Uses

Used in Immunology Research:
BMS-345541 is used as an IκB kinase (IKK) complex inhibitor for studying its effects on interferon-γ (IFN-γ) production by natural killer (NK) cells. This helps researchers understand the role of IKK in immune cell activation and the regulation of cytokine production.
Used in Oral Health Research:
BMS-345541 is used as an IKK inhibitor for studying its effects on the expression of eotaxin and monocyte chemoattractant protein-1 (MCP-1) mRNA in gingival fibroblasts. This application aids in investigating the involvement of IKK in the regulation of inflammatory mediators in oral health and disease.
Used in Cancer Research:
BMS-345541 is used as a nuclear factor κB (NF-κB) pathway inhibitor for studying its effects on tumor necrosis factor α (TNFα) production in human oral squamous carcinoma cells. This research is crucial for understanding the role of NF-κB in cancer progression and identifying potential therapeutic targets for cancer treatment.

Biological Activity

bms-345541 is a highly selective inhibitor of ikk-1 and ikk-2 with ic50 values of 4μm and 0.3μm, respectively [1].bms-345541 is a highly selective inhibitor of ikk that inhibits nf-κb-dependent transcription of pro-inflammatory cytokines both in vitro and in vivo. this specificity is proved in the assay measuring the ikk-2-catalyzed phosphorylation of gst-iκb. in this assay, bms-345541 fails to inhibit other serine/threonine and tyrosine kinases. this selectivity is also evident in cells, only the stimulus-induced phosphorylation of iκb was inhibited by bms-345541 whereas other signal transduction cascades were unaffected [1].since the ikk/ nfκb pathway is important for viability of leukemic cells and is a predictor of relapse in t-all, bms-345541 is tested in some t-all cell lines. it is found that bms-345541 can induce apoptosis and an accumulation of cells in the g2/m phase of the cell cycle. bms-345541 can be used in combination with traditional therapies to overcome resistance to chemotherapeutic agents [2].

Biochem/physiol Actions

BMS-345541 possesses anti-inflammatory properties. It also blocks the nuclear factor κB (NF-κB)-dependent transcription of pro-inflammatory cytokines. BMS-345541 possesses anti-inflammatory activity and plays a role in arresting bone erosion in certain animal models.

references

[1] james r. burke, mark a. pattoli, kurt r. gregor, patrick j. brassil, john f. macmaster, kim w. mcintyre, xiaoxia yang, violetta s. iotzova, wendy clarke, joann strnad, yuping qiu and f. christopher zusi. bms-345541 is a highly selective inhibitor of iκb kinase that binds at an allosteric site of the enzyme and blocks nf-κb-dependent transcription in mice. j. biol. chem. 2003, 278:1450-1456.[2] francesca buontempo, francesca chiarini, daniela bressanin, giovanna tabellini, fraia melchionda, andrea pession, milena fini, luca m. neri, james a. mccubrey and alberto m. martelli. activity of the selective iκb kinase inhibitor bms-345541 against t-cell acute lymphoblastic leukemia. cell cycle. 2012, 11 (13): 2467-2475.

InChI:InChI=1/C14H17N5.ClH/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);1H

Upstream product

• 445430-58-0 4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a) quinoxaline 

Relevant academic research and scientific papers

Imidazoquinoxaline compound for the treatment of melanoma

The present invention concerns a (4(2′-aminoethyl)amino-1,8-dimethylimididazo(1,2-a)quinoxaline)-4,5-dihydro-1,8-dimethylimidazo(1,2-a)quinoxalin-4-one-2-carboxylic acid (BMS-345541) or an analog thereof for the treatment of melanoma cancer. This compound inhibits NFκB activity and expression, and induces apoptosis in melanoma cancer cells. The present invention also provides a method for assaying for the inhibition of melanoma cancer cell growth.