iκbα phosphorylation

BAY 11-7082 (BAY 11-7821) is an NF-κB inhibitor that suppresses TNFα-induced IκBα phosphorylation (IC50=10 μM) and also inhibits the ubiquitin-specific proteases USP7 and USP21 (IC50=0.19 0.96 μM).

Urolithin B is one of the gut microbial metabolites of ellagitannins and is found in diverse plant foods, including pomegranates, berries, walnuts, tropical fruits, and medicinal herbs. Urolithin B inhibits NF-κB activity by reducing the phosphorylation and degradation of IκBα, and suppresses the phosphorylation of JNK, ERK, and Akt, and enhances the phosphorylation of AMPK. Urolithin B is also a regulator of skeletal muscle mass. Urolithin B has anti-inflammatory and antioxidant effects.

Bay 11-7085 can irreversibly inhibit the IκBα phosphorylation induced by TNFα (IC50: 10 μM).

Wedelolactone (IKK Inhibitor II) inhibits NF-κB-mediated gene transcription in cells by blocking the phosphorylation and degradation of IκBα.

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

GS143 is a selective IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. It suppresses NF-κB activation and transcription of target genes without inhibiting proteasome activity. GS143 has anti-asthm[atic] properties.

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.

Rubiadin-1-methyl ether (Rubiadin 1-methyl ether) is a natural product.It inhibits osteoclastic bone resorption via inhibition on the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decrease in the nuclear translocation of p65.

NSC663627 is an IκBα phosphorylation inhibitor.

Potent inhibitor of NF-κB activation (IC50 = 85 nM); decreases IκBα phosphorylation. Attenuates LPS-induced nitric oxide production and expression of TNF-α, IL-6 and MCP. Suppresses proliferation of HeLa and HCT116 cells. Anti-inflammatory and antitumor. Hu et al (2007) Regulation of c-Src nonreceptor tyrosine kinase activity by bengamide A through inhibition of methionine aminopeptidases. Chem.Biol. 14 764 PMID:17656313 |Johnson et al (2012) Myxobacteria versus sponge-derived alkaloids: the bengamide family identified as potent immune modulating agents by scrutiny of LC-MS ELSD libraries. Bioorg.Med.Chem. 20 4348 PMID:22705020 |Kinder et al (2001) Synthesis and antitumor activity of ester-modified analogues of bengamide B. J.Med.Chem. 44 3692 PMID:11606134

Anti-inflammatory agent 6 exhibits anti-inflammatory potential by blocking the phosphorylation of Iκb kinase α β (IKKα β), IκBα and nuclear factor kB p65 (NF-κb p65), which are key controllers of inflammation.

TNF-α-IN-11 (Compound 10) is a TNF-α inhibitor with a dissociation constant (K D) of 12.06 μM. It impedes TNF-α-induced caspase activation and the NF-κB signaling pathway by binding to TNF-α, suppressing the phosphorylation of IκBα and the nuclear migration of NF-κB p65. This compound is utilized in the study of TNF-α-mediated autoimmune diseases [1].

Narasin (sodium salt) (HainanMycin) induces tumor necrosis factor-related apoptosis-induced ligand (TRAIL)-mediated apoptosis by ER stress in glioma cells and inhibits NF-κB signaling by suppressing the phosphorylation of IκBα.

NF-κB-IN-4 (compound 17) is a potent inhibitor of the NF-κB pathway that can cross the blood-brain barrier (BBB). It exhibits potential anti-neuroinflammatory activity with low toxicity, making it suitable for researching neuroinflammation-related diseases. NF-κB-IN-4 can block IκBα activation and phosphorylation, reduce NLRP3 expression, and thereby inhibit NF-κB activation [1].

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].

Eurycomalactone is a natural product isolated from Eurycoma longifolia Jack., acts as a potent NF-κB inhibitor( IC50 of 0.5 μM). Eurycomalactone inhibits protein synthesis, depletes cyclin D1, but does not affect TNFα-induced degradation of IκBα or the phosphorylation of IKKα β and IκBα.

(±)-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.

Inactivation of the tumor suppressor p53 commonly coincides with increased signaling through NF-κB in cancer. CAY10681 is a dual modulator of p53-MDM2 interaction and NF-κB signaling. It potently binds MDM2 (Ki = 250 nM), reducing MDM2-mediated turnover of p53. CAY10681 also inhibits phosphorylation of IκBα and dose-dependently reduces nuclear accumulation of p65. It blocks the proliferation of cancer cell lines (IC50s range from 33 to 37 μM). CAY10681 exhibits excellent oral bioavailability and inhibits tumor growth in A549 xenografts in nude mice.

Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM and an IC50 value of 0.109 μM. It tightly binds to TNF-α, blocking its interaction with TNFR1, and has potential for TNF-α mediated inflammatory and autoimmune disease research [1].

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.