NF-κβ activator 1 is a potent activator of the NF-κβ signaling pathway, with an EC₅₀ value of 0.9μM, NF-κβ activator 1 can induce the expression of superoxide dismutase (SOD2) mRNA[1-2]. By activating the NF-κβ pathway, NF-κβ activator 1 is involved in regulating inflammatory responses and immune cell functions. NF-κβ activator 1 can be used in research related to inflammatory diseases and immune-related disorders [3-4].
In vitro, PC3 prostate cancer cells overexpressing MGLL were pretreated with NF-κβ activator 1 (1μM) for 6h, followed by incubation with Docetaxel (10nM) for 48h. NF-κβ activator 1 significantly reversed the inhibitory effects of MGLL overexpression on NF-κβ p65 phosphorylation and nuclear translocation, restored the expression of senescence-associated secretory phenotype (N-SASP) factors such as IL6 and CXCL8, and attenuated the suppression of cell proliferation induced by the combination of MGLL overexpression and Docetaxel[5]. In PC12 neuronal-like cells, pretreatment with NF-κβ activator 1 (1μM) for 6h, followed by treatment with the CX3CR1 inhibitor AZD8797 (1μM) for 12h, reversed the AZD8797-induced inhibition of NF-κβ pathway proteins p-IκB and p-p65 expression and restored the expression level of the 5-hydroxytryptamine receptor 2A (5-HTR2a)[6].
References:
[1] Mathew B, Ruiz P, Dutta S, et al. Structure-activity relationship (SAR) studies of N-(3-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (SRI-22819) as NF-ҡB activators for the treatment of ALS. Eur J Med Chem. 2021 Jan 15;210:112952.
[2] He Y, Song W, Deng Y, et al. Liraglutide promotes osteogenic differentiation of mesenchymal stem cells by inhibiting M1 macrophage polarization and CXCL9 release in vitro. Mol Cell Endocrinol. 2025 Feb 1;597:112441.
[3] Wang S, Li F, Zhang L, et al. HMGB1 inhibits the IFN-γ-induced PD-L1 expression in NSCLC. J Immunol. 2025 Sep 1;214(9):2480-2488.
[4] Wu W, Yue S, Wang X, et al. Docosahexaenoic acid mitigates experimental autoimmune prostatitis by inhibiting Th17 cell differentiation via the PPARγ/NF-κB/IL-17A pathway. Clin Exp Immunol. 2025 Jan 21;219(1):uxaf055.
[5] Yu J, Zhang M, Li T, et al. Monoacylglycerol lipase blockades the senescence-associated secretory phenotype by interfering with NF-κB activation and promotes docetaxel efficacy in prostate cancer. Oncogene. 2024 Sep;43(38):2835-2849.
[6] Pei J, Zou Y, Wan C, et al. CX3CR1 mediates motor dysfunction in mice through 5-HTR2a. Behav Brain Res. 2024 Mar 12;461:114837.
NF-κβ activator 1是一种有效的NF-κβ信号通路激活剂，其EC50值为0.9μM，并可诱导超氧化物歧化酶（SOD2）mRNA的表达[1-2]。NF-κβ activator 1通过激活NF-κB通路，参与调节炎症反应及免疫细胞功能，NF-κβ activator 1可用于炎症性疾病及免疫相关疾病的相关研究[3-4]。
在体外，NF-κβ activator 1（1μM）预处理MGLL过表达的PC3前列腺癌细胞6小时，随后使用Docetaxel（10nM）孵育细胞48小时，NF-κβ activator 1显著逆转MGLL过表达对NF-κβ p65磷酸化及核转位的抑制作用，并恢复IL6、CXCL8等衰老相关分泌表型（N-SASP）因子的表达，同时削弱MGLL过表达联合Docetaxel对细胞增殖的抑制效果[5]。NF-κβ activator 1（1μM）处理PC12神经元样细胞6小时，随后使用CX3CR1抑制剂AZD8797（1μM）孵育12h，NF-κβ activator 1可逆转AZD8797对NF-κβ通路蛋白p-Iκβ及p-p65表达的抑制，并恢复5-羟色胺受体2A（5-HTR2a）的表达水平[6]。