nf-κb

AP-1/NF-κB activation inhibitor 1 is a potent inhibitor of AP-1 and NF-κB mediated transcriptional activation (IC50 = 1 μM), without blocking basal transcription driven by the β-actin promoter. It has a similar inhibitory effect on the production of IL-2 and IL-8 levels in stimulated cells [1].

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.

NF-κB-IN-18 (Compound 5k) is an orally active NF-κB inhibitor that suppresses the phosphorylation of p65 and demonstrates significant anti-inflammatory activity in mice with xylene-induced ear edema.

NF-κB/MAPK-IN-2 (compound 14) is a potent inhibitor of NF-κB and MAPK pathways. It effectively reduces the protein expression levels of p-p65, p-IκB, p-p38, p-JNK, and p-ERK. This compound decreases the release of TNF-α and IL-6 induced by LPS and inhibits the nuclear translocation of p65 and c-Fos. NF-κB/MAPK-IN-2 shows potential for research in sepsis.

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.

NF-κB/HIF-1α-IN-1 (compound 9c) effectively inhibits the NF-κB activation pathway and demonstrates selective antifibrotic activity. This compound exhibits no significant cytotoxicity in NCI tumor cell lines. In rat models, NF-κB/HIF-1α-IN-1 successfully ameliorates liver fibrosis, suppresses the expression levels of NF-κB and HIF-1α, and induces Nrf2.

NF-κB-IN-14 (compound 5e) inhibits nitric oxide production in macrophages induced by LPS, with an IC50 of 6.4 μM. It disrupts the interaction between TLR4 and MyD88 proteins, thereby inhibiting the NF-κB signaling pathway. Additionally, NF-κB-IN-14 reduces ear edema and inflammation in a mouse model of atopic dermatitis.

NF-κB-IN-15 (compound 14r) is a potent NF-κB inhibitor. It reduces NO levels in LPS-stimulated cells and suppresses the release of IL-6, TNF-α, and IL-1β. Additionally, it hinders LPS-induced p65 phosphorylation and IκBα degradation. NF-κB-IN-15 exhibits anti-inflammatory properties and holds potential for research in acute lung injury (ALI).

Glucocorticoid receptor/NF-κB modulator-1 (Compound 20) is a derivative of ocotillol. It prevents degradation of glucocorticoid receptor (GR) mRNA and GR protein and inhibits the activation of the NF-κB signaling pathway. Additionally, it reduces levels of nitric oxide (NO), interleukin (IL-6), and tumor necrosis factor-alpha (TNF-α), and improves sepsis in mice.

NF-κB-IN-16 (compound 9) is a complex of an NF-κB inhibitor and Cisplatin (Pt(IV) complex) with potent and low-toxicity antitumor activity. It can cause DNA damage, induce mitochondrial dysfunction, generate reactive oxygen species, and trigger apoptosis via mitochondrial pathways and endoplasmic reticulum stress. NF-κB-IN-16 effectively inhibits the NF-κB/MAPK signaling pathway and disrupts PI3K/AKT signal transduction. Additionally, it demonstrates excellent in vivo antitumor efficacy and low toxicity in A549 or A549/CDDP xenograft models.

NF-κBdegrader 1 (Compound MD-1) is an NF-κB1p105 subunit degrader. It exhibits anti-inflammatory properties, with an IC50 of 2.02 μM for inhibiting TNF-α and 5.40 μM for inhibiting NO. NF-κBdegrader 1 induces p105 degradation via the Cullin-RING ligase (CRL) SCFBTCP, thereby inhibiting NF-κB transcriptional activity. This compound shows potential for research in inflammation-related diseases.

STAT3/NF-κB-IN-1 is a potent inhibitor of STAT3 and NF-κB, exhibiting IC50 values of 5.86 μM for STAT3 and 4.22 μM for NF-κB in 4 T1 cells. It induces apoptosis by upregulating key apoptotic regulators (caspases-3, 9, Bax) and downregulating Bcl-2 expression. STAT3/NF-κB-IN-1 shows significant anticancer activity against breast cancer cell lines and can reduce tumor volume in vivo. It is applicable for research in breast cancer.

NF-κB-IN-2 inhibits canonical NF-κB signaling induced by TNF-α in PC-3 cells.

NF-κB-IN-6 (Compound 3d) is an anti-inflammatory agent that suppresses the NF-κB signaling pathway, thereby reducing iNOS and COX-2 protein expression. It inhibits NO production in LPS-induced RAW264.7 cells with an IC50 of 23.1 μM[1].

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].

NF-κB-IN-5 (compound 4d) is an orally active NF-κB inhibitor that interacts directly with NF-κB, and exhibits antitumor activity against human cancer cell lines, with IC50 values of 5.35, 2.81, 2.83, 2.02, and 3.90 μM for HCT116, U87-MG, HepG2, BGC823, and PC9, respectively.

Akt/NF-κB/JNK-IN-1 (Compound 2i) is an inhibitor of the Akt, NF-κB, and JNK signaling pathways, demonstrating inhibition of nitric oxide production (IC50: 3.15 μM) and exhibiting anti-inflammatory effects.

TLR4/NF-κB/MAPK-IN-1 is a novel antineuroinflammatory agent inhibiting the TLR4/NF-κB/MAPK pathways.

NF-κB-IN-3 (Compound 2) is an NF-κB inhibitor with an IC50 of 0.70 μM, and it can be used as an anti-tumour agent.

NF-κB/PON1-IN-1 (Compound 16) is an inhibitor of the NF-κB/PON1 pathway, exhibiting antioxidant activity (IC50: 45.76 μM) and hepatoprotective properties.

NF-κB/MAPK-IN-1 is a potent dual inhibitor of the NF-κB and MAPK pathways with potential anti-inflammatory activity, inhibition of NO production, and inhibition of LPS-induced activation of iNOS, COX-2, ERΚ and P38. NF-κB/MAPK-IN-1 is used for the prevention and treatment of rheumatoid arthritis (RA).

NF-κB-IN-8 is a competitive antagonist of LPS for MD-2 binding, and it impedes the expression of inflammatory factors by engaging MD-2. Additionally, it inhibits ALP activity and is usable in inflammation research, including acute lung injury (ALI) [1].

NF-κB-IN-9, a nuclear factor kappa B (NF-κB) targeting sonosensitizer with excitation and emission wavelengths (λex/λem) of 489/628 nm, features dual resveratrol units that strongly inhibit NF-κB signaling. This compound demonstrates notable anti-tumor properties and pronounced sonocytotoxicity against cancer cells, maintaining biosafety in xenograft mouse models.

NF-κB-IN-10 (compound E1) is an NF-κB inhibitor that mitigates heart failure symptoms by modulating the Nrf2/NF-κB signaling pathway, alleviating oxidative stress and inflammation. It suppresses LPS-induced NO production and downregulates iNOS and COX-2 expression in RAW264.7 cells, showing potential for cardiovascular disease research [1].