ikkβ

IKK-IN-3 is a highly potent and selective inhibitor of IkappaB kinase 2 (IKK2 or IKKβ). It exhibits impressive inhibitory activity against IKK2 (IC50 = 19 nM), while also demonstrating significant efficacy against IKK1 (or IKKα) with an IC50 value of 400 nM.

IKK-IN-4 is a potent and selective inhibitor of IkappaB kinase 2 with IC50 values of 45 nM against IKKβ and 650 nM against IKKα [1].

IKK 16 (IKK Inhibitor VII) is a selective IκB kinase (IKK) inhibitor for IKK-2, IKK complex and IKK-1 with IC50 of 40 nM, 70 nM and 200 nM, respectively.

IKKγ NBD Inhibitory Peptide acetate is a NEMO-binding domain peptide (NBD peptide) acetate corresponding to the NEMO amino-terminal alpha-helical region. IKKγ NBD Inhibitory Peptide acetate is shown to block TNF-alpha-induced NF-kB activation.

IKKβ-IN-1 is a potent, orally active inhibitor of IkappaB (IKK-β) with an IC50 of 0.20 μM. It reduces the inhibition of PGE2 and TNF-α production in murine macrophages and protects mice from infection shock-induced death.

TBK1/IKKε-IN-5 is a dual TBK1 and IKKε inhibitor(IC50 of 1 nM and 5.6 nM, respectively).

TBK1 IKKε-IN-2 is a dual inhibitor of TBK1 and IKKε.

IKKß-IN-124 is an allosteric inhibitor of IκBα phosphorylation and NF-κB transcriptional activity through selective capture of the inactive conformation and hence blockade of IKKβ S177/S181 phosphorylation.

IKKγ NBD Inhibitory Peptide TFA is a specific NF-κB inhibitor that hinders the interaction between the IKKγ NEMO-binding domain (NBD) and IKKα and IKKβ, effectively preventing TNF-α-induced NF-κB activation. It has been demonstrated to significantly suppress inflammation and improve neurological deficits induced by cerebral ischemia [1] [2] [3].

IKK2-IN-4(IKK2 Inhibitor VI) is a highly potent IKK-2 inhibitor with an IC50 value of 25 nM. IKK2-IN-4 inhibited the production of TNF-α in PBMC induced by LPS.

IKK-IN-1 is an inhibitor of IKK ([Ikappa]B kinase), a protein known to regulate the NF-[kappa]B signaling pathway.

TBK1 IKKε-IN-4, a 6-aminopyrazolopyrimidine derivative, serves as a potent, selective inhibitor for TBK1 and IKKε, demonstrating IC50 values of 13 nM and 59 nM, respectively. This compound exhibits significantly reduced activity, by 100- to 1000-fold, against other protein kinases, such as PDK1, PI3K family members, and mTOR[1].

IKK 16 hydrochloride is a selective inhibitor of IKK2 (IC50: 40 nM), the IKK complex (IC50: 70 nM), and IKK1 IκB kinase (IKK) (IC50: 200 nM), as well as leucine-rich repeat kinase-2 (LRRK2; IC50: 50 nM).

TBK1 IKKε-IN-6 (example 110) is a potent inhibitor of TBK1 and IKKε, exhibiting IC50 values below 100 nM for both enzymes.

2-AMINO-5-PHENYL-THIOPHENE-3-CARBOXYLIC is Inhibitior of IKKβ.

ACHP Hydrochloride (IKK-2 Inhibitor VIII) is a highly potent and selective inhibitor of IKK-β with an IC50 of 8.5 nM.

TAK-715 is a p38 MAPK inhibitor for p38α.

Rosmarinic acid (Labiatenic acid) is widely found in plants and has antioxidant, anti-inflammatory, and antibacterial activities. It inhibits MAO-A, MAO-B, and COMT with IC50 of 50.1, 184.6, and 26.7 μM respectively.

INH14 is a novel inhibitor of the IKKα β-dependent TLR inflammatory response (IC50s: 8.97 3.59 μM for IKKα IKKβ).

IMD-0354 (IKK2 Inhibitor V) is an IKKβ inhibitor that blocks IκBα phosphorylation in the NF-κB pathway.

Aniline-d5 is a deuterated compound of Aniline. Aniline has a CAS number of 62-53-3. Aniline has been reported to be toxic to the spleen via iron overload and induction of oxidative stress via Heme Oxygenase 1 up-regulation. Toxicity of this agent on the spleen is characterized by hyperplasia, fibrosis, and vascular congestion in rats. Studies suggest that this compound causes significant increase in both p-IKKα and p-IKKβ which in-turn increases NF-κB and AP-1 binding activity. In other experiments, Aniline displays a capacity to induce methemoglobinemia, glutathione depletion, membrane cytoskeletal changes, loss of circulating blood cells, and adversely affects blood stability.

BI605906 is an IKKβ inhibitor that inhibits tumor necrosis factor alpha-dependent IkappaB degradation and expression of the pro-inflammatory mediator interleukin-6, which can be used to study inflammatory skin diseases such as psoriasis.

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)

StA-IFN-1 is an inhibitor of the interferon (IFN) induction pathway with an IC50 value of 4.1 μM in a GFP reporter assay for IFN induction similar to TPCA-1 , which specifically inhibits the IKKβ component of the IFN induction pathway. It does not show inhibitory activity in a GFP reporter assay for IFN signaling in which ruxolitinib , which is specific for the IFN signaling component JAK1, is active. StA-IFN-1 reduces the levels of IFN-β, but not ISG MxA, mRNA, suggesting that it is selective for the IFN induction pathway and not the IFN signaling pathway.

Bay 65-1942 (R form) is the less active enantiomer of Bay 65-1942, a selective and ATP-competitive IKKβ inhibitor.

Bay 65-1942 free base is an ATP-competitive and selective inhibitor of IKKβ.

F1, an anti-inflammatory peptide, incorporates the HIV-1 Tat protein transduction domain linked with a 15-amino acid sequence from residues 46-60 of the inhibitor of NF-κB kinase-interacting peptide (IKIP). It effectively blocks LPS-induced phosphorylation of IκB kinase α (IKKα) and IKKβ, along with the nuclear translocation of NF-κB (p65) in mouse peritoneal macrophages at 5 µM concentration. F1, administered at 5 mg/kg in vivo, significantly reduces IL-6, TNF-α, and IL-1β serum levels and enhances survival in a mouse sepsis model induced by LPS.

Rhein-13C4 is intended for use as an internal standard for the quantification of rhein by GC- or LC-MS. Rhein is an anti-inflammatory anthraquinone found in rhubarb and is the bioactive derivative of its prodrug diacerein . At 10 μM, rhein inhibits IL-1β signaling, suppressing signaling through NF-κB, and reduces the expression of the matrix metalloproteases MMP-1 and MMP-13.1 It inhibits IKKβ (IC50 = 11.8 μM), decreasing iNOS and IL-6 expression in LPS-stimulated macrophages but paradoxically increasing TNF-α, IL-1β, and HMBG1 expression.2 Rhein shows efficacy against pancreatic fibrosis, chronic pancreatitis, and hyperglycemia-induced pancreatic β-cell apoptosis.3,4 It also inhibits angiogenesis of breast cancer cells under normoxic and hypoxic conditions.5

BMS-066 is an IKKβ Tyk2 pseudokinase inhibitor with IC50s of 9 nM and 72 nM, respectively.

MLN120B is a selective and ATP competitive IKKβ inhibitor (IC50: 60 nM).

1-Dehydro-[10]-gingerdione inhibits IKKβ activity by targeting its activation loop, thereby preventing IKKβ-mediated phosphorylation of IκBα in macrophages stimulated by agonists. Furthermore, this compound suppresses LPS-induced NF-κB transcriptional activity, highlighting its potential in research related to NF-κB-associated inflammation and autoimmune disorders [1].

IKKβ inhibitor

Cyclo(L-Pro-L-Val), a 2,5-diketopiperazine extracted from the fruits of Mycobacterium chiliolyticum AZ2 and Mycobacterium leprae, possesses anti-inflammatory activity and virulence activity against phytopathogenic microorganisms (e.g., R. fascians LMG 3605) and inhibits Gram-positive plant pathogens.Cyclo(L-Pro-L-Val) significantly inhibited IKKα phosphorylation and IκBα and NF-κB activation as well as iNOS and COX-2 activation in a concentration Cyclo(L-Pro-L-Val) significantly inhibited the phosphorylation of IKKα, IKKβ, IκBα, and NF-κB, as well as the activation of iNOS and COX-2 in a concentration-dependent manner, and is a potential therapeutic agent for the treatment of inflammation-related diseases.

(±)-Nutlin-3 blocks the interaction of p53 with its negative regulator Mdm2 (IC50 = 90 nM), inducing the expression of p53-regulated genes and blocking the growth of tumor xenografts in vivo. CAY10682 is a pyrrolo[3,4c]pyrazole derivative that inhibits the p53-Mdm2 interaction as potently as (±)-nutlin-3 (Ki = 83 nM) and also dose-dependently reduces activation of the NF-κB pathway. It specifically prevents phosphorylation of IκBα by the kinases IKKα, IKKβ, and IKK (IC50s = 80.5, 78.2, and 57.1 μM, respectively). CAY10682 blocks the growth of cancer cells in vitro (IC50s = 2-6 μM) and inhibits the growth of A549 cell xenografts in mice without significantly reducing body weight.

SR 12460 is a mimetic of the IκB kinase β (IKKβ) NEMO/IKKγ-binding domain (NBD) that inhibits the protein-protein interaction between the IKK complex subunits NF-κB essential modulator (NEMO/IKKγ) and IKKβ.1It inhibits TNF-α-induced NF-κB activation in a reporter assay when used at concentrations ranging from 25 to 150 μM. It reduces LPS-induced production of IL-6 in RAW 264.7 cells. SR 12460 (30 mg/kg) improves grip strength in themdxmouse model of Duchenne muscular dystrophy. 1.Zhao, J., Zhang, L., Mu, X., et al.Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-kB activationPLoS Biol.16(6)e2004663(2018)

Bay 65-1942 hydrochloride is an ATP-competitive and selective inhibitor of IKKβ.

Ac2-26 ammonium, an N-terminal peptide of annexin 1, exhibits anti-inflammatory properties, reduces IKKβ protein levels in lysosomes via chaperone-mediated autophagy (CMA), improves lung ischemia-reperfusion injury outcomes, and mitigates airway inflammation and hyperresponsiveness in an asthma rat model [1] [2] [3] [4].

HPN-01 (IKK inhibitor XII) is a selective IKK inhibitor that inhibits IKK-α, IKK-β, and IKK-ε. HPN-01 reduces the severity of the disease, attenuates the immune imbalance, and prolongs the lifespan of mice in a model of autoimmune encephalomyelitis, and can be used to study immune disorders.

MLN120B dihydrochloride (ML120B dihydrochloride) is a highly potent, orally active inhibitor of IKKβ, competitively binding to ATP with an IC50 value of 60 nM, effectively suppressing the growth of multiple myeloma cells in vitro and in vivo, and valuable in rheumatoid arthritis research.