19542-67-7 Usage
Description
BAY 11-7082 is a potent and selective inhibitor of the NF-kB signaling pathway, which plays a crucial role in regulating immune responses, inflammation, and cell survival. It works by irreversibly inhibiting the TNF-α-inducible phosphorylation of IκBα, resulting in decreased expression of NF-κB and adhesion molecules. BAY 11-7082 is cell permeable and has been widely used as a research tool to investigate the role of NF-κB in various physiological and pathophysiological processes.
Uses
Used in Pharmaceutical and Biomedical Research:
BAY 11-7082 is used as a nuclear factor-kappa B (NF-kB) inhibitor for studying the role of NF-kB activation in various cellular processes and diseases. Its application in this field helps researchers understand the molecular mechanisms underlying inflammation, immune responses, and cell survival.
Used in Immunology and Inflammation Studies:
BAY 11-7082 is used as an anti-inflammatory agent to investigate the action of the NF-kB signaling pathway in the production of interleukin (IL)-8 and other inflammatory mediators. This helps in understanding the role of NF-kB in inflammatory processes and identifying potential therapeutic targets for treating inflammatory diseases.
Used in Cancer Research:
BAY 11-7082 is used as a tool to study the role of NF-kB activation in Mycoplasma hyorhinis-induced epithelial-mesenchymal transition (EMT) and cell migration. This helps researchers explore the connection between NF-kB signaling and cancer progression, as well as the potential of BAY 11-7082 as a therapeutic agent in cancer treatment.
Used in Transplantation Research:
BAY 11-7082 is used as a nod-like receptor family pyrin domain containing 3 (NLRP3) selective inhibitor to examine its effects on liver inflammation in mice after hematopoietic stem cell transplantation. This application aids in understanding the role of NLRP3 inflammasomes in transplantation-related complications and the potential of BAY 11-7082 in mitigating these issues.
Biological Activity
Irreversible inhibitor of TNF- α -stimulated I κ B α phosphorylation (IC 50 ~ 10 μ M); leads to decreased NF- κ B and subsequent decreased expression of adhesion molecules. Also reversibly activates MAP kinases and stimulates apoptosis.
Biochem/physiol Actions
Bay 11-7082 acts as a selective inhibitor for nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway. In addition, to the inhibition of nuclear factor-kappa B (NF-kB), Bay 11-7082 also triggers apoptosis in anucleated erythrocytes, human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines and primary adult T-cell leukemia cells.
Enzyme inhibitor
This protein kinase inhibitor (FW = 207.31 g/mol; CAS 19542-67-7; lmax = 251 nm), also named 3-[(4-methylphenyl)sulfonyl]-(2E)-propenenitrile, targets NF-κB activation, selectively and irreversibly blocking TNF-α- induced phosphorylation of IκB-α without affecting phosphorylation of constitutive IκB-α. Mechanism of Inhibitory Action: NF-κB transcription factor regulates expression of inflammatory cytokines, various chemokines and immunoreceptors, as well as cell adhesion molecules. When stationed within the cytoplasm, NF-κB is kept inactive through its binding to the inhibitory factor IκB; however, certain stimuli result in IκB phosphorylation and ubiquitin-mediated degradation, freeing NF-κB for translocation to the nucleus. In endothelial cells, IκB-α phosphorylation and degradation occur within 15 min of TNFα treatment, allowing NF-κB to translocate to the nucleus to activate gene expression. Treatment of humnan vascular endothelial cells (HUVEC) with TNFα results in rapid loss of IκB-α from the cytoplasm. BAY11-7082 stabilizes IκB-α in a dose-dependent manner (IC50 ≈ 10 μM). There is a clear correlation between the concentration of drug that stabilizes IκB-α, the concentration that inhibits nuclear levels of NF-κB, and the concentration that inhibits adhesion molecule expression. More recent studies demonstrate that BAY 11- 7082 prevents ubiquitin conjugation to Ubc13 and UbcH7 by forming a covalent adduct with their cysteine residues via Michael addition at the C-3 atom of BAY 11-7082, followed by the release of 4-methylbenzenesulfinate. BAY 11-7082 stimulated Lys48-linked polyubiquitin chain formation in cells and protected Hypoxia-Inducible Factor-1α (HIF1α) from proteasomal degradation, suggesting it inhibits the proteasome. These results indicate that the anti-inflammatory effects of BAY 11-7082, its ability to induce B-cell lymphoma and leukemic T-cell death and to prevent the recruitment of proteins to sites of DNA damage are exerted via inhibition of components of the ubiquitin system– not by inhibiting NF-κB. BAY11-7082 also inhibits proliferation and promotes apoptosis in breast carcinoma MCF-7 cells by inhibiting phosphorylation of ATP citrate lyase.
References
1) Pierce et al. (1997) Novel inhibitor of cytokine-induced IkBα phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo; J. Biol. Chem., 272 21096
2) Park et al. (2009) 4-hydroxyestradiol induces anchorage-independent growth of human mammary epithelial cells via activation of IkappaB kinase: potential role of reactive oxygen species; Cancer Res., 69 2416
3) Miyamoto et al. (2010) Inhibitor of IkappaB kinase activity, BAY 11-7082, interferes with interferon regulatory factor 7 nuclear translocation and type I interferon production by plasmacytoid dendritic cells; Arthritis Res. Ther., 12 R87
4) Xu et al. (2019) Bay 11-7082 facilitates wound healing by antagonizing mechanical injury – and TNF-α-induced expression of MMPs in posterior cruciate ligament; Connect. Tissue Res. 60 311
5) Kim et al. (2018) TNF-α induces human neural progenitor cell survival after oxygen-glucose deprivation by activating the NFκB pathway; Exp. Mol. Med., 50 14
Check Digit Verification of cas no
The CAS Registry Mumber 19542-67-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,9,5,4 and 2 respectively; the second part has 2 digits, 6 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 19542-67:
(7*1)+(6*9)+(5*5)+(4*4)+(3*2)+(2*6)+(1*7)=127
127 % 10 = 7
So 19542-67-7 is a valid CAS Registry Number.
InChI:InChI=1/C10H9NO2S/c1-9-3-5-10(6-4-9)14(12,13)8-2-7-11/h2-6,8H,1H3/b8-2+
19542-67-7Relevant articles and documents
PROCESS FOR THE PREPARATION OF ARYLSULFONYLPROPENENITRILES
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Page/Page column 9, (2020/06/01)
The present invention relates to a process for the preparation of arylsulfonylpro- penenitriles. The reaction starting from arylsulfonyl halides is catalyzed by a cat- alyst compound comprising a transition metal. The process is scalable, environ- mentally benign and provides the product in good yield.
PROCESS FOR THE PREPARATION OF ARYLSULFONYLPROPENENITRILES BY PHOTOCATALYTIC REACTIONS
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Page/Page column 8, (2019/03/17)
The present invention relates to a process for the preparation of arylsulfonylpro- penenitriles. The reaction starting from arylsulfonyl iodides is catalyzed by light. The process is scalable, environmentally benign and provides the product in good yield.
An improved synthesis of vinyl- and β-iodovinyl sulfones by a molecular iodine-mediated one-pot iodosulfonationdehydroiodination reaction
Sawangphon, Tassaporn,Katrun, Praewpan,Chaisiwamongkhol, Korbua,Pohmakotr, Manat,Reutrakul, Vichai,Jaipetch, Thaworn,Soorukram, Darunee,Kuhakarn, Chutima
supporting information, p. 1692 - 1707 (2013/05/22)
An improved one-pot method to synthesize vinyl sulfones from unsaturated systems by using molecular iodine/sodium arenesulfinate/sodium acetate as reagents was described. Vinyl sulfones derived from styrene derivatives were generally obtained in good to excellent yields except for those bearing strong electron releasing substituent. Aliphatic alkenes and activated alkenes gave the corresponding vinyl sulfone products in moderate to good yields. Arylacetylenes yielded the respective β-iodovinyl sulfones in good yields while low yield was observed with aliphatic terminal alkyne. The potentials of the method entail simplicity, short reaction time, non-anhydrous reaction conditions, employing inexpensive, non-metallic reagent and integrating two reactions that are commonly accomplished separately into a single operation. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file. Copyright Taylor & Francis Group, LLC.