tlr4 signaling

TC-E 5003 (NSC-30176) is a selective inhibitor of PRMT1 with IC50 of 1.5 μM.

IAXO-102 is a TLR4 antagonist that negatively regulates TLR4 signaling by inhibiting MAPK and p65 NF-κB phosphorylation, as well as the expression of TLR4-dependent proinflammatory proteins. It also prevents the development of experimental abdominal aortic aneurysm.

Resatorvid (TAK-242), a selective Toll-like receptor 4 (TLR4) inhibitor, binds directly to Cys747 to prevent TLR4-TIRAP interaction, thereby blocking downstream signaling. Resatorvid exhibits antitumor, anti-inflammatory, and neuroprotective activities.

RV01 is a novel quinoline-substituted analogue of resveratrol that inhibits DNA damage, reduces ethanol-induced acetaldehyde dehydrogenase (ALDH2) mRNA expression, and has hydroxyl radical scavenging activity. rV01 reduces iNOS expression and has anti-neuroinflammatory effects. rV01 reduces tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion. RV01 reduced tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion, inhibited lps-induced ROS production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, decreased toll-like receptor 4 (TLR4) protein expression, and inhibited lps-induced activation of mitogen-activated protein kinase (MAPK) and nuclear transcription factor-кB (NF-кB) signaling pathways.

RC529-MDP is an immunological adjuvant that couples Toll-like receptors (TLR4a) and NOD-like receptors (NOD2a) to enhance the innate immune response through the TLR4 and NOD2 signaling pathways. In mouse models, RC529-MDP induces high levels of the cytokine interleukin-related factor (IL-6), highlighting its immunostimulatory activity. Additionally, when injected into mice models with ovalbumin (OVA), RC529-MDP elevates OVA-specific antibody responses, T cell responses, and the proportion of memory T cells.

BI1543673 is an inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4). It can diminish inflammatory responses in human lung tissue stimulated by TLR4 and TLR7/8. Additionally, BI1543673 reduces inflammatory signaling in a mouse lung inflammation model induced by LPS.

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.

Fosfenopril (Fosinoprilat) is a potent angiotensin-converting enzyme (ACE) inhibitor that mitigates lipopolysaccharide-induced inflammation in monocytes through the suppression of TLR4/NF-κB signaling pathways, and Fosfenopril is utilized in cardiovascular and anti-inflammatory research to investigate molecular mechanisms of ACE inhibition.

Nitric oxide production-IN-11k is a compound that inhibits TLR4, JNK, and NF-κB signaling pathways. It suppresses nitric oxide (NO) production in LPS-stimulated RAW264.7 cells, with an IC₅₀ of 23.2 µM. By downregulating TLR4 expression and reducing the phosphorylation level of JNK, Nitric oxide production-IN-11k inhibits the activation of NF-κB, thereby blocking the transcription of inflammation-related genes. This leads to decreased expression of iNOS and COX-2, and consequently reduces the production of inflammatory mediators such as NO, PGE₂, and TNF-α, exerting anti-inflammatory effects. Nitric oxide production-IN-11k shows potential application value in the study of rheumatoid arthritis and other inflammatory diseases.

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.

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.

NGI-235 is a selective OST-A inhibitor that specifically inhibits the NF-κB inflammatory signaling pathway by blocking TLR4 glycosylation and cell surface localization. NGI-235 can be used in research on inflammatory and immune-related diseases.

AHR agonist 10 is a potent activator of the AHR pathway (EC50 = 2.01 nM). It enhances transcription of key downstream target genes of AHR, such as CYP1A1 and CYP1B1, while reducing the expression of CD36 and IL-18, and demonstrates low cytotoxicity in normal cells (> 40 μM). This compound inhibits the expression of CCL5, CCL20, IL-6, IL-8, S100A9, TLR4, TNF-α, and TNFR1, indicating its effective regulation of inflammatory responses via AHR-dependent signaling. AHR agonist 10 is applicable in psoriasis research [1].

ETI60 is an orally active selective TLR inhibitor that targets the nucleoside-binding sites I of TLR7 (IC50 = 0.68 μM) and TLR9 (IC50 = 0.12 μM) without affecting surface TLRs (including TLR1/TLR2, TLR2/TLR6, TLR4, and TLR5). It demonstrates nanomolar activity in cell-based, biophysical, and in vivo assays, effectively inhibiting endosomal TLR-mediated pro-inflammatory signaling. ETI60 modulates the expression of genes related to inflammation and significantly improves symptoms in mouse models of psoriasis and systemic lupus erythematosus (SLE). ETI60 is applicable in studies related to autoimmune and inflammatory diseases.

ETI41 is an orally active selective TLR inhibitor that targets the nucleoside-binding site I of TLR7 (IC50= 0.63 μM) and TLR9 (IC50= 0.16 μM), without affecting surface TLRs (including TLR1/TLR2, TLR2/TLR6, TLR4, and TLR5). It demonstrates nanomolar activity in cell-based, biophysical, and in vivo studies, effectively inhibiting endosomal TLR-mediated pro-inflammatory signaling. ETI41 suppresses the expression of inflammation-related genes and significantly improves symptoms in mouse models of psoriasis and systemic lupus erythematosus (SLE). ETI41 is applicable in research related to autoimmune and inflammatory diseases.

β-Funaltrexamine (β-FNA) is a selective, irreversible antagonist of the μ opioid receptor (μopioid receptor) with anti-inflammatory and neuroprotective properties. It reduces TLR4 signaling, inhibits cytokine-induced iNOS activation and neuroinflammation, and improves neuronal degeneration. Additionally, β-Funaltrexamine suppresses NF-κB signaling and chemokine expression in human astrocytes and mice. This compound is utilized in research for neurodegenerative diseases, such as stroke.

D-Mannuronic Acid is a uronic acid monosaccharide widely utilized in the manufacturing of alginate polymers. D-Mannuronic Acid has applications in the study of cancer biology due to its structural and biochemical relevance in carbohydrate-based processes, as well as its utility as a biochemical building block in glycobiology and biomaterials research.

Semapimod tetrahydrochloride (CPSI-2364 tetrahydrochloride) is a synthetic ornithine mitogen-activated protein kinase blocker and pro-inflammatory cytokine production inhibitor that interferes with macrophage and microglia function. Sematimod tetrahydrochloride inhibits TLR4 signaling, TNF-α, IL-1β, and IL-6, and is used in the study of Crohn's disease and other inflammatory conditions.

KOdiA-PC is a truncated oxidized phospholipid and a CD36-targeting ligand found on oxLDL. It inhibits activation of TLR4 signaling components.

Polygalasaponin F has anti-neuroinflammatory activity, can inhibit the release of inflammatory cytokines TNF-α and NO induced by lipopolysaccharides (LPS) and reduce the expression of inducible nitric oxide synthases. Polygalasaponin F can significantly i

L48H37 is a chemically stable analog of Curcumin. It exhibits potent inhibitory properties against myeloid differentiation protein 2 (MD2), acting as a specific inhibitor. Its mechanism involves inhibiting the interaction and signaling transduction of LPS-TLR4/MD2. L48H37 is primarily utilized in sepsis and lung injury research [1].

1. Atractylenolide-I has an anti-inflammatory effect by inhibiting TNF-α and IL-6 production; ameliorates sepsis syndrome, liver and kidney functions by reduction of pro-inflammatory cytokines and LPS. 2. Atractylenolide-I significantly sensitizes the res

2,4,5-Trimethoxybenzoic acid (Asaronic acid) is a natural product that inhibits M1 macrophage phenotype-induced inflammatory responses and suppresses TLR4/IL-6-mediated activation of NF-κB and JAK-STAT signaling pathways.