NF-κB-IN-1 (1,6-Heptadiene-3,5-dione, 1,7-bis(3,4-dimethoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methylene]-, (1E,6E)-) is a potent NF-κB signaling pathway inhibitor. It is a 4-arylidene crucumin analogue. NF-κB-IN-1 directly inhibits IKK to block NF-κB activation. NF-κB-IN-1 effectively inhibits the viability of lung cancer cells and attenuates the clonogenic activity of A549 cells.

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

Akt/NF-κB/MAPK-IN-1 (compound 2m) serves as a potent, orally active inhibitor targeting NO with an IC50 of 7.70 μM and demonstrates low toxicity. This compound exerts anti-inflammatory effects by impeding the Akt/NF-κB and MAPK signaling pathways [1].

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

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).

Akt/NF-κB/JNK-IN-1 (Compound 2i) is an inhibitor of Akt, NF-κB and JNK signalling pathways.Akt/NF-κB/JNK-IN-1 exhibits an inhibitory effect on nitric oxide production (IC50: 3.15 μM) and shows anti-inflammatory effects.

Triacetylresveratrol (Acetyl-trans-resveratrol) has anti-cancer activity,it inhibits the phosphorylation of STAT3 and NFκB, down-regulates Mcl-1, and up-regulates Bim and Puma in pancreatic cancer cells.

5-Aminosalicylic Acid (5-ASA) is an anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE.

AP-1/NF-κB activation inhibitor 1 is a potent inhibitor of AP-1 and NF-κB mediated transcriptional activation ( IC 50 =1 μM), does not blocking basal transcription driven by the β-actin promoter. AP-1/NF-κB activation inhibitor 1 has a similar inhibitory effect on the production of IL-2 and IL-8 levels in stimulated cells [1].

1. 6-Shogaol (6-Shogaol) has antipyretic and analgesic effects in addition to inhibitory effect on lipoxygenase activity. 2. 6-shogaol has anti-inflammatory property, reduces the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats. 3. 6-Shogaol inhibits the growth of human cancer cells and induces apoptosis in COLO 25 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). 4. 6-Shogaol effectively inhibit invasion and metastasis of hepatocellular carcinoma through diverse molecular mechanisms, including inhibition of the MAPK and PI3k/Akt pathways and NF-κB and STAT3 activities to suppress expression of MMP-2/-9 and uPA and block angiogenesis, could further regulate urokinase-type plasminogen activity.

Kanzonol D, a flavonoid derived from the hairy root cultures of Glycyrrhiza glabra [1], exhibits anti-inflammatory and anticancer properties by inhibiting nitric oxide production and suppressing NF-κB activation. It also shows potential in osteoblast differentiation, suggesting its utility in bone diseases.

MyD88-IN-1 is a potent MyD88 inhibitor MyD88-IN-1 has anti-inflammatory activity and inhibits downstream inflammatory signaling pathways, including the NF-κB pathway, of members of the Toll-like receptor (TLR) and interleukin-1 (IL-1) receptor family MyD88-IN-1 may be used for the study of cancer and the treatment of inflammation.

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid peptide hormone produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland, as well as in keratinocytes, astrocytes, monocytes, and gastrointestinal cells.1It is an agonist of melanocortin receptor 3 (MC3R) and MC4R that induces cAMP production in Hepa cells expressing the human receptors (EC50s = 0.16 and 56 nM, respectively).2α-MSH (100 pM) reducesS. aureuscolony formation andC. albicansgerm tube formationin vitro.3It inhibits endotoxin-, ceramide-, TNF-α-, or okadaic acid-induced activation of NF-κB in U937 cells.1α-MSH reduces IL-6- or TNF-α-induced ear edema in mice.4It also prevents the development of adjuvant-induced arthritis in rats and increases survival in a mouse model of septic shock. Increased plasma levels of α-MSH are positively correlated with delayed disease progression and reduced death in patients with HIV.1 1.Catania, A., Airaghi, L., Colombo, G., et al.α-melanocyte-stimulating hormone in normal human physiology and disease statesTrends Endocrinol. Metab.11(8)304-308(2000) 2.Miwa, H., Gantz, I., Konda, Y., et al.Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptorsJ. Pharmacol. Exp. Ther.273(1)367-372(1995) 3.Cutuli, M., Cristiani, S., Lipton, J.M., et al.Antimicrobial effects of a-MSH peptidesJ. Leukoc. Biol.67(2)233-239(2000) 4.Lipton, J.M., Ceriani, G., Macaluso, A., et al.Antiiinflammatory effect of the neuropeptide a-MSH in acute, chronic, and systemic inflammationAnn. N.Y. Acad. Sci.25(741)137-148(1994)

β5i-IN-1 is a selective inhibitor of β5i, exhibiting potent activity with an IC50 of 8.463 nM. It modulates immune responses by promoting the release of TNF-α and IL-6 and affecting NF-κB transcriptional activity. This compound has applications in the research of idiopathic pulmonary fibrosis [1].

AAA is an antagonist of G protein-coupled receptor 75 (GPR75).1It increases basal GPR75 protein levels and inhibits 20-HETE-induced reductions in GPR75 protein levels in PC3 cells. AAA (5 and 10 μM) also reduces 20-HETE-induced phosphorylation of EGFR, NF-κB, and Akt in, and cell migration of, PC3 cells.In vivo, AAA (10 mg/kg per day) reduces systolic blood pressure, albuminuria, renal angiotensin II levels, and cardiac hypertrophy in a Cyp1a1-Ren-2 transgenic rat model of malignant hypertension when administered prior to induction or after establishment of hypertension.2 1.Cárdenas, S., Colombero, C., Panelo, L., et al.GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cellsBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(2)158573(2020) 2.Sedláková, L., Kikerlová, S., Husková, Z., et al.20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic ratsBiosci. Rep.38(5)BSR20171496(2018)

Receptor for advanced glycation end products (RAGE) antagonist. Blocks S100P, S100A4 and HMGB-1 mediated RAGE activation in vitro and in vivo. Inhibits growth and metastasis of rat glioma tumors. Reduces cell growth and RAGE-mediated NF-κB activity in hum

Streptazolin is a fungal metabolite originally isolated from S. viridochromogenes. It increases NF-κB activity when used at concentrations ranging from 60 to 130 μg/ml, at least in part, via PI3K signaling. Streptazolin enhances TNF-α secretion induced by LPS and enhances IL-8 secretion when used alone or in combination with LPS in THP-1 Blue cells.

IR-Crizotinib is a conjugate of the near-infrared dye IR-786 and Crizotinib, an NF-κB-inducing kinase (NIK) inhibitor, with an IC50 of 3.381 μM for intracranial glioblastoma (GBM) localization in mice. It has the ability to cross the blood-brain barrier and fluorescently mark GBM, and demonstrates efficacy in inhibiting glioma proliferation and invasion both in vitro and in vivo, making it significant in cancer research [1].

HMGB1-IN-2 (compound 15) is a selective inhibitor of the highly conserved nuclear protein HMGB1, demonstrating no inhibitory effect at an IC50 of 20.2 μM in RAW264.7 cells. At a concentration of 30 μM, HMGB1-IN-2 reduces IL-1β, TNF-α, and caspase-1 p20 levels, and inhibits NF-κB p65 phosphorylation, providing anti-apoptotic effects. In vivo, HMGB1-IN-2 at a dose of 15 mg/kg administered intraperitoneally alleviates kidney injury in a mouse model of septic acute kidney injury. Furthermore, it inhibits Huh7 and A549 cells with IC50 values of 77.0 μM and 82.0 μM, respectively [1].

1. Schisandrol B (Besigomsin) may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways. 2. Schisandrol B has anti-inflammatory property, potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. 3. Schisandrol B induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway. 4. Schisandrol B significantly inhibits cell proliferation in a dose-dependent manner, due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation.

1. Phellodendrine (Phallodendrin) has anti-nephritic activity, may be due to its ability to inhibit the proliferation or the migration of macrophages and cytotoxic T lymphocytes in the glomeruli.

1. Peimine (Wanpeinine A) has good anti-inflammatory effects in vivo. 2. Peimine is an inhibitor to inhibit LPS-induced production of inflammatory cytokines by blocking the MAPKs and NF-κB signaling pathway.

1. β,β-Dimethylacrylshikonin (Dimethylacrylshikonin) is a promising agent for developing an improved strategy for radiotherapy against tumors. (a) Injection of Dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. (b) Dimethylacrylshikonin significantly suppressed the growth of H(22) transplantable hepatoma, and induced the activation of caspase-3 . (c) Dimethylacrylshikonin inhibited growth of gastric cancer SGC-791 cells by inducing ERK signaling pathway. 2. Dimethylacrylshikonin inhibits the proliferation of MCF-7 cells in vitro by inducing apoptosis through the downregulation of Bcl-2, upregulation of Bax and partial inactivation of the NF-κB pathway.

NSC-37445 has anti-tumor activity, such as inhibits growth of bladder tumor cells in a nude mice model , prevents the recurrence and progression of non-muscle-invasive urothelial cell carcinoma. NSC-37445 can significantly reduce the expression of CDK1-inhibitory kinases, Myt1 and Wee1, and cause cyclin B1 protein accumulation leading to CDK1 activation in T24 cells. 3. Flavokawain A (Flavokavain A) may exert anti-inflammatory responses by suppressing LPS-induced expression of pro-inflammatory mediators via blockage of NF-κB-AP-1-JNK/p38 MAPK signaling pathways in the murine macrophages.

1. Monotropein (Monotropeine) has antinociceptive action. 2. Monotropein has anti-apoptosis and anti-catabolic activity in chondrocytes. 3. Monotropein has anti-inflammatory action by inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic role in colitis. 4. Monotrope ininhibit the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) mRNA in LPS-induced RAW 264.7 macrophages.

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.

Sulfuretin is a potent anti-oxidant, has protective effect against t-BHP-induced oxidative damage in human liver-derived HepG2 cells is attributable to its ability to scavenge ROS and up-regulate the activity of HO-1 through the Nrf2/ARE and JNK/ERK signa

Mollugin (Rubimaillin) may be a JAK2 inhibitor and inhibits LPS-induced inflammatory responses by blocking the activation of the JAK-STAT pathway. Mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF- κ B. Mollugin may be a novel therapeutic candidate for bone loss-associated disorders including osteoporosis, rheumatoid arthritis, and periodontitis. Also, it has anticancer efficacy, can modulate the HER2 pathway in HER2-overexpressing Y cells with a potential role in the treatment and prevention of human breast and ovarian Y with HER2 overexpression.

1. Dehydrodiisoeugenol has anti-inflammatory activity. (1). Dehydrodiisoeugenol inhibited the expression of the COX-2 in RAW264.7 murine macrophages stimulated with LPS. (2). Dehydrodiisoeugenol inhibited LPS-stimulated phosphorylation-dependent proteolys

IQ-1S free acid (IQ-1S) is an effective and specific c-Jun N-Terminal Kinase Inhibitor. IQ-1S inhibits murine delayed-type hypersensitivity. IQ-1S can reduce inflammation and cartilage loss associated with CIA and can serve as a small-molecule modulator for mechanistic studies of JNK function in rheumatoid arthritis. IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH.

HMGB1-IN-1 (compound 6) exhibits potent inhibition of NO production in RAW264.7 cells, with an IC50 of 15.9 ± 0.6 μM, and effectively disrupts the HMGB1/NF-κB/NLRP3 signaling pathway. This compound demonstrates promising anti-inflammatory and anti-sepsis properties, particularly in the context of renal injury [1].

EP12, a c-Myc inhibitor and G4 stabilizer, induces apoptosis and DNA damage in multiple myeloma cells while obstructing P65/P50 nuclear translocation by disrupting the NF-κB signaling pathway, effectively inhibiting multiple myeloma growth [1].

COX-2-IN-32 (Compound 2f) is a dual inhibitor of iNOS and COX-2, known to downregulate NF-κB expression. Demonstrating anti-inflammatory properties, it impedes NO production in LPS-induced RAW264.7 macrophages with an IC50 value of 11.2 μM [1].

Gastric inhibitory peptide (GIP) (22-51), a pro-atherogenic peptide comprised of 30 amino acids from the residues 22-51 of its precursor protein proGIP, is present in human plasma. It activates the degradation of IκB-α and the nuclear translocation of NF-κB in both macrophage-differentiated THP-1 cells and human aortic endothelial cells at a concentration of 1 µM. Additionally, in ApoE-/- mice, GIP (22-51) escalates the area of atherosclerotic lesions and plaque development in vivo.

Aniline-d5 is a deuterated compound of Aniline. Aniline has a CAS number of 62-53-3. Aniline has been reported to be toxic to the spleen via iron overload and induction of oxidative stress via Heme Oxygenase 1 up-regulation. Toxicity of this agent on the spleen is characterized by hyperplasia, fibrosis, and vascular congestion in rats. Studies suggest that this compound causes significant increase in both p-IKKα and p-IKKβ which in-turn increases NF-κB and AP-1 binding activity. In other experiments, Aniline displays a capacity to induce methemoglobinemia, glutathione depletion, membrane cytoskeletal changes, loss of circulating blood cells, and adversely affects blood stability.

HD-TAC7, a potent PROTAC HDAC degrader, exhibits IC50 values of 3.6 μM, 4.2 μM, and 1.1 μM for HDAC1, HDAC2, and HDAC3, respectively. It effectively decreases NF-κB p65 in RAW 264.7 macrophages and is utilized in research targeting inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD) [1].

Ac2-26 TFA, the active N-terminal peptide of Annexin A1 (AnxA1), mitigates ischemia-reperfusion-induced acute lung injury, reduces AnxA1 protein expression, and inhibits the activation of NF-κB and MAPK pathways in affected lung tissue [1].

Glucocorticoid receptor modulator 1 is a potent, orally active, non-steroidal selective glucocorticoid receptor modulator, exhibiting IC50 values of 9 nM and 130 nM against NF-κB and AP-1, respectively. It effectively reduces the expression of inflammatory factors such as IL-6, IL-1β, and TNF-α, and alleviates dermatitis in mice.

(5E)-7-Oxozeaenol is a resorcylic acid lactone that has been found in the fungus MSX 63935 and has enzyme inhibitory and anticancer activities.1,2 It inhibits TGF-β-activated kinase 1 (TAK-1; IC50 = 1.3 μM).1 (5E)-7-Oxozeaenol inhibits proliferation of MCF-7, H460, SF-268, HT-29, and MDA-MB-435 human cancer cells with IC50 values of 4.9, 1.2, 5.6, 4.4, and 5.5 μM, respectively.2 |1. Fakhouri, L., El-Elimat, T., Hurst, D.P., et al. Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues. Bioorg. Med. Chem. 23(21), 6993-6999 (2015).|2. Ayers, S., Graf, T.N., Adcock, A.F., et al. Resorcylic acid lactones with cytotoxic and NF-κB inhibitory activities and their structure-activity relationships. J. Nat. Prod. 74(5), 1126-1131 (2011).

1. Prunetin (Prunusetin) significantly reduces serum levels of inflammatory cytokines and mortality in mice challenged with lipopolysaccharide. 2. Prunetin mediates anti-obesity/adipogenesis effects by suppressing obesity-related transcription through a feedback mechanism that regulates the expression of adiponectin, adipoR1, adipoR2, and AMPK. 3. Prunetin and biochanin A are potent reducers of NF-κB and ERK activation, zonula occludens 1 tyrosine phosphorylation, and metalloproteinase-mediated shedding activity, which may account for the barrier-improving ability of these isoflavones. 4. Prunetin significantly suppresses ATP-induced mucin secretion from cultured RTSE cells; Prunetin inhibits the production of MUC5AC mucin protein induced by EGF or PMA from NCI-H292 cells; Prunetin also inhibits the expression of MUC5AC mucin gene induced by EGF or PMA from NCI-H292 cells.

CMC2.24 (TRB-N0224) is an orally active tricarbonylmethane agent that demonstrates effectiveness in inhibiting Ras activation and the downstream effector ERK1/2 pathway, thus effectively combating pancreatic tumor formation in mice. Additionally, CMC2.24 exerts potent inhibitory effects on zinc-dependent MMPs, with IC50s ranging from 2.0-69 μM. Furthermore, CMC2.24 aids in alleviating the progression of osteoarthritis by restoring cartilage homeostasis and inhibiting chondrocyte apoptosis through the NF-κB/HIF-2α axis[1][2][3].

1. beta-Asarone (Cis-Isoelemicin) may be a potential preventive drug for Alzheimer's disease. 2. Beta-Asarone prevents autophagy and synaptic loss by reducing ROCK expression in SAMP8 mice. 3. The co-administration of beta-Asarone(Cis-Isoasarone) and l-dopa may contribute to the treatment of 6-OHDA-induced damage in rats by inhibiting autophagy activity. 4. Beta-Asarone exhibits anti-inflammatory effects by suppressing the production of pro-inflammatory mediators through NF-κB signaling and the JNK pathways in activated microglial cells and might be developed as a promising candidate to treat various neuroinflammatory diseases.

1. Cucurbitacin IIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. 2. Cucurbitacin IIb exhibits its anti-inflammatory activity through modula

NF-κΒ activator 1 can activate the nf-kappa Β gene activator, EC50 of 0.9 microns. NF-κΒ is widely used in eukaryotic cells as a gene regulating cell proliferation and cell survival. NF-κΒ activator 1 induces superoxide dismutase (SOD) 2 1 mRNA expression.

1. Ginsenoside Rk3 and Rh4 could have a role in treating inflammatory diseases. 2. Ginsenoside Rk3 is often used as a major ingredient of the compound preparation for ischemic heart diseases.

1. Decursin (Decursinol angelate) is able to attenuate kainic acid-induced seizures and could have potential as an antiepileptic drug. 2. Decursin exhibits hepatoprotective effects , potentially by inhibiting the TGF-β1 induced NOX activation and Smad signaling. 3. Decursin has anti-cancer activity , mediated suppression of the PKCα, MAPK and NF-κB pathways in MCF-7 cells. 4. Decursin exhibits cytotoxicity against various human cancer cells and to possess anti-amnesic activity in vivo through the inhibition of AChE activity.

Aloenin aglycone (compound 13), an inhibitor of NF-κB, can be sourced from aloe exudate. It impedes TNFα-stimulated NF-κB transcriptional activity, showing an IC 50 of 18.7 μM. At a concentration of 10 μM, aloenin aglycone decreases both inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule 1 (ICAM-1) gene expression in HepG2 cells exposed to 10 ng/mL TNFα [1].

(−)-N-Hydroxyapiosporamide (NHAP), an alkaloid, serves as an NF-κB inhibitor and demonstrates significant antitumor activity both in vitro and in vivo. It has potential applications in colorectal cancer (CRC) research [1].

TNF-α-IN-11 (Compound 10) is a TNF-α inhibitor exhibiting a dissociation constant (K D) of 12.06 μM. By binding to TNF-α, it impedes TNF-α-induced caspase activation and the NF-κB signaling pathway. Additionally, it suppresses 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].

NCI 126224, a toll-like receptor 4 (TLR4) antagonist, demonstrates selective inhibition of nitric oxide (NO) production in RAW 264.7 macrophages, triggered by the TLR4 agonist LPS (IC50 = 0.31 µM), as opposed to minimal effects on NO production induced by agonists for TLR7/8 (R-848), TLR1/2 (Pam3CSK4), and TLR3 (poly(I:C)). Nevertheless, it also effectively inhibits NO production initiated by the TLR2/6 agonist FSL-1 at an IC50 of 0.6 µM in the same cell line. Moreover, NCI 126224 suppresses LPS-induced NF-κB activity in BV-2 microglial cells and reduces LPS-triggered increases in IL-1β and TNF-α levels in RAW 264.7 macrophages with IC50 values of 5.92, 0.42, and 1.54 µM, respectively.