nf-κb signaling pathway

LT052 is a selective and efficient BET BD1 inhibitor with anti-inflammatory activity. It mediates the BRD4 NF-κB NLRP3 inflammatory signaling pathway and can be used in gout arthritis research.

NSC-697923 (2-[(4-methylphenyl)sulfonyl]-5-nitrofuran), a potent inhibitor of UBE2N (ubiquitin-conjugating enzyme E2 N, Ubc13), exhibits its role in inducing cell death in neuroblastoma (NB) cells through two distinct mechanisms. In p53 wild-type NB cells, NSC-697923 promotes the nuclear importation of p53, thereby triggering cell death. Meanwhile, in p53 mutant NB cells, NSC-697923 activates the JNK-mediated apoptotic pathway, leading to cell death. Additionally, NSC-697923 inhibits DNA damage and NF-κB signaling, further contributing to its antitumor activity.

N,N-Dimethylacetamide (DMAc) is a drug excipient with blood-brain barrier permeability and anti-inflammatory activity, acting through inhibition of the NF-κB signaling pathway. N,N-Dimethylacetamide can reduce endotoxin-induced inflammatory responses in vivo.

Scutellarin (Scutellarein-7-glucuronide), an active flavone isolated from Scutellaria baicalensis, can inhibit RANKL-mediated MAPK and NF-κB signaling pathway in osteoclasts, and down-regulate the STAT3 Girdin Akt signaling in HCC cells.

Ethyl gallate (gallic acid ethyl ester) obviously decreases cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner, exhibits cytotoxicity in a dose-dependent manner. Ethyl gallate can inhibit the abilities of invasion of breast cancer in vitro by inhibiting the mRNA levels of MMP-9 MMP-2, phosphorylation of Akt and protein expression of NF-κB and inhibits hydrogen peroxide signaling, may represent an alternative class of vasopressors for use in septic shock. Also, Ethyl gallate suppresses proliferation and invasion in human breast cancer cells by modulating the PI3K Akt pathway, which may contribute to inhibiting their downstream targets such as NF-κB p-65, Bcl-2 Bax, and mRNA levels of MMP-2 and MMP-9 in breast cancer cells, could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy.

ethyl 2-[3,5-bis(trifluoromethyl)phenyl]-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxylate is a synthetic compound belonging to the curcumin family. It is involved in the regulation of immune response and inflammation through inhibition of the NF-κB signaling pathway, in the regulation of antioxidant response through activation of the Nrf2 signaling pathway, and in the regulation of cell survival and proliferation through inhibition of the Akt signaling pathway.

(E/Z)-BCI (NSC-150117), a dual-specificity phosphatase 6 (DUSP6) inhibitor with anti-inflammatory properties, reduces LPS-induced inflammatory mediators and ROS production in macrophage cells by activating the Nrf2 signaling axis and inhibiting the NF-κB pathway.

Radicicol (Monorden) is an antifungal antibiotic and a potent inhibitor of heat shock protein 90 (Hsp90), which leads to the degradation of Hsp90 by the proteasome by binding to its ATP-binding pocket. In addition, Radicicol inhibits the growth and proliferation of several tumor cell lines. It also has anti-malarial activity and acts as an inhibitor of adipose- and obesity-related proteins (FTO). Radicicol inhibits iNOS gene expression by blocking the p38 kinase signaling pathway and NF-kB/Rel

TH023 is an inhibitor of the TLR4 signaling pathway, specifically targeting the formation of TLR4 homodimers. In HEK-Blue hTLR4 cells, TH023 suppresses the secretion of embryonic alkaline phosphatase with an IC50 of 0.354 μM and inhibits NO expression in RAW264.7 cells, with an IC50 of 1.61 μM. Additionally, TH023 inhibits the activation of NF-κB and reduces the nuclear translocation of NF-κB p65. The compound demonstrates anti-inflammatory effects in a mouse model of LPS-induced acute sepsis and improves lung injury in mice.

TLR4 NF-κB-IN-1 (Compound 7x) is an orally bioavailable inhibitor targeting the TLR4 NF-κB signaling pathway, with anti-inflammatory properties and the ability to cross the blood-brain barrier. It can alleviate LPS-induced acute neuroinflammation in mice and downregulate the protein expression of TLR4, P-NF-κB, and P-IκB-α.

FKK6 is a selective agonist of the pregnane X receptor (PXR) with an EC50 of 1.2 µM. It demonstrates strong affinity for plasma proteins and exhibits favorable metabolic characteristics in human microsomes. FKK6 inhibits the PXR-related NF-κB signaling pathway, reducing the expression of inflammatory factors and showing anti-inflammatory activity in a mouse model of DSS-induced colitis.

Tubulin MMP-IN-3 (Compound 15j) is a dual inhibitor of tubulin polymerization and MMP, effectively inhibiting MMP-2 and MMP-9 with IC50 values of 21.13 μM and 19.24 μM, respectively. It disrupts the NF-κB signaling pathway, leading to mitochondrial dysfunction and mitochondrial-dependent apoptosis. Tubulin MMP-IN-3 shows antiproliferative activity in various cancer cells by causing cell cycle arrest at the G2 M phase and demonstrates antitumor effects in mouse models.

Antioxidant agent-20 (Compound 3d) exhibits potent anti-inflammatory and antioxidant activities. It reduces reactive oxygen species (ROS) and apoptosis in a dose-dependent manner. Antioxidant agent-20 demonstrates photoprotective effects on UVB-exposed human skin keratinocytes (HaCaT) (IC50=5.13 µM) by activating Nrf2 HO-1 signaling and inhibiting the NF-κB pathway.

CB1R antagonist 2 (Compound 11g) functions as an antagonist of the cannabinoid receptor 1 (CB1R), inhibiting the MAPK NF-κB signaling pathway and exhibiting anti-inflammatory properties. In RAW264.7 cells, it suppresses LPS-induced expression of IL-6, IL-1β, and TNF-α. In murine models, it improves OVA-induced allergic rhinitis.

NF-κB-IN-19 (Compound 8) is an NF-κB inhibitor. It effectively induces DNA damage in tumor cells through the NF-κB signaling pathway and promotes the production of reactive oxygen species (ROS), as well as induces autophagy and apoptosis. Additionally, NF-κB-IN-19 inhibits levels of VEGF and HIF-1α, exerting antiproliferative effects in tumor cells through the PI3K AKT and STAT-3 pathways. It is also effective in overcoming cisplatin resistance and exhibits antitumor activity.

Anti-inflammatory agent 97 (Compound 1l) is an anti-inflammatory compound and also inhibits oxidative stress. It can reduce colon shortening and alleviate inflammatory symptoms in a mouse model of ulcerative colitis induced by DSS. Additionally, it modulates the inflammation-associated TLR4/NF-κB signaling pathway and the oxidative stress-related Nrf2/HO-1 signaling pathway.

NLRP3-IN-76 is an orally active NLRP3 inhibitor that suppresses the production of NO and reduces the mRNA levels of pro-inflammatory cytokines (iNOS, IL-6, IL-1β, and TNFα). It exerts anti-inflammatory effects by inhibiting the activation of the NLRP3 inflammasome and the NF-κB signaling pathway. Furthermore, NLRP3-IN-76 can ameliorate DSS-induced colitis and is applicable for studying inflammatory bowel disease (IBD).

(S,R,S)-AHPC-Boc derivative 1 (Compound 80-9; VH032-Boc derivative 1) is a selective proteasomal degrader targeting MALT1, which recruits the E3 ubiquitin ligase CRBN to form a ternary complex with MALT1. This interaction leads to the ubiquitination and subsequent proteasomal degradation of MALT1. By disrupting the CBM complex, (S,R,S)-AHPC-Boc derivative 1 inhibits the NF-κB signaling pathway and shows potential in inducing apoptosis in ABC-DLBCL cells. It holds promise for research into MALT1-dependent cancers, such as diffuse large B-cell lymphoma (DLBCL).

PROTACSTING degrader-3 (Compound ST9) is a STINGPROTAC-type degrader with a DC50 of 0.62 μM. It induces STING degradation via the ubiquitin-proteasome pathway. This compound exerts anti-inflammatory effects by inhibiting the STING/TBK1/NF-κB signaling. Additionally, it offers renal protection and can be used in research on acute kidney injury.

Anti-inflammatory agent 102 (Compound 11a) is an orally effective anti-inflammatory compound. It exerts its effects by inhibiting the activation of the ASK1/p38 MAPKs/NF-κB signaling pathway. This agent displays significant anti-inflammatory activity by suppressing the release of NO, ROS, and inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Anti-inflammatory agent 102 is applicable in research concerning inflammatory diseases, including ulcerative colitis (UC).

RS47 is a potent and specific inhibitor of the non-canonical NF-κB signaling pathway, with a Kd value of 1.1 μM, acting by blocking the binding of RelB to target DNA. Studies indicate that RS47 can inhibit the growth of colorectal cancer (CRC) cells and B lymphomas, making it a promising research tool for targeting cancers driven by hyperactive non-canonical NF-κB signaling.

CAY10526 (BTH) is a selective mPGES-1 inhibitor that acts as an inhibitor of the NF-κB signaling pathway.

MHY884 is an inhibitor of tyrosinase that acts by inhibiting UVB-induced activation of the NF-κB signaling pathway through the downregulation of oxidative stress.

CL075 (3M002) is a selective TLR8 agonist with immunomodulatory activity, triggering the MyD88-dependent signaling pathway and activating NF-κB and IRF7 to elicit the production of inflammatory cytokines and type I interferon (IFN).