iκbα phosphorylation

BAY 11-7082 (BAY 11-7821) 是一种 NF-κB 抑制剂，可抑制 TNFα 诱导的 IκBα 磷酸化 (IC50=10 μM)。BAY 11-7082 也是一种泛素特异性蛋白酶 USP7 和 USP21 的抑制剂 (IC50=0.19 0.96 μM)。

Urolithin B 是一种 ellagitannins 的肠道微生物代谢产物，具有抗炎和抗氧化作用。它也是骨骼肌质量的调节因子，通过减少 IκBα 的磷酸化和降解来抑制 NF-κB 活性，并抑制 JNK、ERK 和 Akt 的磷酸化，并增强 AMPK 的磷酸化。

Bay 11-7085 抑制NF-κB 激活和IκBα磷酸化，其稳定 IκBα 的IC50值为 10 μM。

Wedelolactone (IKK Inhibitor II) 是来自旱莲草的一种天然产物，通过阻断 IκBα 的磷酸化和降解来抑制细胞中 NF-κB 介导的基因转录，具有抗癌，抗炎和抗氧化活性。

IMD-0354 (IKK2 Inhibitor V) 是一种选择性IKKβ抑制剂，能够抑制 NF-κB 活性。它能够抑制 TNF-α 诱导的 NF-κB 转录活性，IC50=1.2 μM。

Cyclo(L-Pro-L-Val) 是从辣椒溶杆菌AZ2和白斑分枝杆菌果实中提取出的 2,5-二酮哌嗪，具有抗炎活性，对植物病原微生物 (如 R. fascians LMG 3605) 具有毒性活性，能抑制革兰氏阳性植物病原菌。Cyclo(L-Pro-L-Val) 以浓度依赖性方式显著抑制了IKKα、IKKβ、IκBα和NF-κB 的磷酸化以及iNOS 和COX-2的活化，是治疗炎症相关疾病的潜在治疗剂。

Narasin (sodium salt) (HainanMycin) 通过神经胶质瘤细胞中的 ER 应激诱导肿瘤坏死因子相关凋亡诱导配体 (TRAIL) 介导的细胞凋亡，并通过抑制 IκBα 的磷酸化来抑制 NF-κB 信号传导。

Nafamostat是一种合成丝氨酸蛋白酶抑制剂，也是一种血液透析的抗凝血剂，通过上调TNFR1的表达诱导细胞凋亡，通过阻断 IκBα磷酸化抑制NF-κB 活性,能够抑制SARS-CoV-2和COVID-19。

GS-143 是选择性的IκBα泛素化抑制剂，抑制 SCFβTrCP1介导的IκBα泛素化作用，IC50=5.2 μM。GS143 抑制NF-κB 的活化和靶基因的转录，并且不抑制蛋白酶体的特性，并具有抗哮喘作用。

NSC663627 is an IκBα phosphorylation inhibitor.

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.

(±)-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.

Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM. Benpyrine tightly binds to TNF-α and blocks its interaction with TNFR1, with an IC50 value of 0.109 μM. Benpyrine has the potential for TNF-α mediated inflammatory and autoimmune disease research[1]. Benpyrine (5-20 μM; 14 hours; RAW264.7 cells) pretreatment results in a dose-dependent decrease in the phosphorylation of IκBα in RAW264.7 cells (stimulated with 10 ng mL TNF-α or 1 μg mL LPS). Benpyrine abolishes the TNF-α-induced nuclear translocation of NF-κB p65 in RAW264.7 cells[1].Benpyrine only blocks cell death induced by TNF-αWT and Y119A, and increases the cell survival rate up to 80%. Benpyrine does not obviously affect L57A- and Y59L-induced cytotoxicity in L929 cells[1]. Benpyrine (25-50 mg kg; oral gavage; daily; for 2 weeks; Balb c mice) treatment significantly relieves the symptoms of collagen-induced arthritis. Benpyrine dose-dependently decreases the levels of proinflammatory cytokines, such as IFN-γ, IL-1β and IL-6, and increases the concentration of the anti-inflammatory cytokine IL-10[1].Endotoxemia murine model shows that Benpyrine (25 mg kg) could attenuate TNF-α-induced inflammation, thereby reducing liver and lung injury[1]. [1]. Weiguang Sun, et al. Discovery of an Orally Active Small Molecule TNF-α Inhibitor. J Med Chem. 2020 Jul 15.

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

Rubiadin-1-methyl ether (Rubiadin 1-methyl ether) 是一种巴戟天中的蒽醌类化合物，能够抑制 NF-κB p65 的磷酸化和 IκBα 的降解以及减少 p65 的核转位，阻碍破骨细胞的骨吸收。

NF-κB-IN-4 (化合物 17) 是有效的NF-κB 通路抑制剂，可透过血脑屏障(BBB)。NF-κB-IN-4 具有潜在的抗神经炎症活性，毒性低，可用于研究神经炎症相关疾病。NF-κB-IN-4 可阻断 IκBα 的活化及磷酸化，降低 NLRP3 的表达，从而抑制NF-κB 的激活。

Anti-inflammatory agent 6 能够阻断作为炎症关键控制器的 Iκb 激酶 α β（IKKα β）、IκBα 和核因子 kB p65（NF-κb p65）的磷酸化，表现出抗炎潜力。

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.

1-Dehydro-[10]-gingerdione 通过靶向IKKβ的激活环直接抑制 IKKβ 活性，从而破坏用激动剂刺激的巨噬细胞中 IKKβ 催化的 IκBα 磷酸化。1-Dehydro-[10]-gingerdione 抑制 LPS 诱导的NF-κB 转录活性。1-Dehydro-[10]-gingerdione 具有用于NF-κB 相关炎症和自身免疫性疾病研究的潜力。

TNF-α-IN-11 (Compound 10)是一种TNF-α抑制剂, KD值为12.06 μM。该化合物通过结合TNF-α并阻断其诱发的caspase和NF-κB信号通路激活，来实现其抑制作用。其具体机制包括抑制IκBα磷酸化和NF κB p65的核转位，适用于研究TNF-α介导的自身免疫性疾病。

Eurycomalactone 是一种NF-κB 抑制剂，IC50=0.5 μM，是一种天然产物。它可抑制蛋白合成，降低 cyclin D1 蛋白水平，但对 TNFα 诱导的 IκBα 降解或 IKKα β 和 IκBα 的磷酸化水平没有作用。